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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Current advancements and potential strategies in the development of MERS-CoV vaccines</title><author><name sortKey="Zhang, Naru" sort="Zhang, Naru" uniqKey="Zhang N" first="Naru" last="Zhang">Naru Zhang</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University,</institution><addr-line>Shanghai,</addr-line><country>China</country></nlm:aff></affiliation></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24766432</idno><idno type="pmc">4241375</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241375</idno><idno type="RBID">PMC:4241375</idno><idno type="doi">10.1586/14760584.2014.912134</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001325</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001325</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Current advancements and potential strategies in the development of MERS-CoV vaccines</title><author><name sortKey="Zhang, Naru" sort="Zhang, Naru" uniqKey="Zhang N" first="Naru" last="Zhang">Naru Zhang</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="AFF0002"><institution>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University,</institution><addr-line>Shanghai,</addr-line><country>China</country></nlm:aff></affiliation></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation><nlm:aff id="AFF0001"><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></nlm:aff></affiliation></author></analytic><series><title level="j">Expert Review of Vaccines</title><idno type="ISSN">1476-0584</idno><idno type="eISSN">1744-8395</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the <italic>in vivo</italic> efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Mishra, N" uniqKey="Mishra N">N Mishra</name></author><author><name sortKey="Olival, K" uniqKey="Olival K">K Olival</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Al Dhahiry, Sh" uniqKey="Al Dhahiry S">SH Al Dhahiry</name></author><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balkhair, A" uniqKey="Balkhair A">A Balkhair</name></author><author><name sortKey="Al Maamari, K" uniqKey="Al Maamari K">K Al Maamari</name></author><author><name sortKey="Alawi, Fb" uniqKey="Alawi F">FB Alawi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mailles, A" uniqKey="Mailles A">A Mailles</name></author><author><name sortKey="Blanckaert, K" uniqKey="Blanckaert K">K Blanckaert</name></author><author><name sortKey="Chaud, P" uniqKey="Chaud P">P Chaud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guery, B" uniqKey="Guery B">B Guery</name></author><author><name sortKey="Poissy, J" uniqKey="Poissy J">J Poissy</name></author><author><name sortKey="El Mansouf, L" uniqKey="El Mansouf L">L el Mansouf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author><author><name sortKey="Folkers, Gk" uniqKey="Folkers G">GK Folkers</name></author><author><name sortKey="Fauci, As" uniqKey="Fauci A">AS Fauci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R McBride</name></author><author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Lam, Cs" uniqKey="Lam C">CS Lam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Hartwig, Ng" uniqKey="Hartwig N">NG Hartwig</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yip, Cc" uniqKey="Yip C">CC Yip</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhong, N" uniqKey="Zhong N">N Zhong</name></author><author><name sortKey="Zheng, B" uniqKey="Zheng B">B Zheng</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D Niemeyer</name></author><author><name sortKey="Zillinger, T" uniqKey="Zillinger T">T Zillinger</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name></author><author><name sortKey="Yount, Bl" uniqKey="Yount B">BL Yount</name></author><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hurst, Kr" uniqKey="Hurst K">KR Hurst</name></author><author><name sortKey="Ye, R" uniqKey="Ye R">R Ye</name></author><author><name sortKey="Goebel, Sj" uniqKey="Goebel S">SJ Goebel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z Lou</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonavia, A" uniqKey="Bonavia A">A Bonavia</name></author><author><name sortKey="Zelus, Bd" uniqKey="Zelus B">BD Zelus</name></author><author><name sortKey="Wentworth, De" uniqKey="Wentworth D">DE Wentworth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, K" uniqKey="Wu K">K Wu</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Peng, G" uniqKey="Peng G">G Peng</name></author><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peng, G" uniqKey="Peng G">G Peng</name></author><author><name sortKey="Sun, D" uniqKey="Sun D">D Sun</name></author><author><name sortKey="Rajashankar, Kr" uniqKey="Rajashankar K">KR Rajashankar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, X" uniqKey="Zhu X">X Zhu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Farzan, M" uniqKey="Farzan M">M Farzan</name></author><author><name sortKey="Harrison, Sc" uniqKey="Harrison S">SC Harrison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X Shi</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hofmann, H" uniqKey="Hofmann H">H Hofmann</name></author><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K Pyrc</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Moore, Mj" uniqKey="Moore M">MJ Moore</name></author><author><name sortKey="Vasilieva, N" uniqKey="Vasilieva N">N Vasilieva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Rajashankar, Kr" uniqKey="Rajashankar K">KR Rajashankar</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name></author><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, L" uniqKey="Lu L">L Lu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pak, Je" uniqKey="Pak J">JE Pak</name></author><author><name sortKey="Sharon, C" uniqKey="Sharon C">C Sharon</name></author><author><name sortKey="Satkunarajah, M" uniqKey="Satkunarajah M">M Satkunarajah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prabakaran, P" uniqKey="Prabakaran P">P Prabakaran</name></author><author><name sortKey="Gan, J" uniqKey="Gan J">J Gan</name></author><author><name sortKey="Feng, Y" uniqKey="Feng Y">Y Feng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hwang, Wc" uniqKey="Hwang W">WC Hwang</name></author><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y Lin</name></author><author><name sortKey="Santelli, E" uniqKey="Santelli E">E Santelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="The Spike Protein Of, Sars" uniqKey="The Spike Protein Of S">SARS- The spike protein of</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Donaldson, Ef" uniqKey="Donaldson E">EF Donaldson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Bottazzi, Me" uniqKey="Bottazzi M">ME Bottazzi</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zakhartchouk, An" uniqKey="Zakhartchouk A">AN Zakhartchouk</name></author><author><name sortKey="Sharon, C" uniqKey="Sharon C">C Sharon</name></author><author><name sortKey="Satkunarajah, M" uniqKey="Satkunarajah M">M Satkunarajah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazán</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML DeDiego</name></author><author><name sortKey="Sola, I" uniqKey="Sola I">I Sola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cao, Z" uniqKey="Cao Z">Z Cao</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Chan, C" uniqKey="Chan C">C Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Lu, H" uniqKey="Lu H">H Lu</name></author><author><name sortKey="Siddiqui, P" uniqKey="Siddiqui P">P Siddiqui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, F" uniqKey="Song F">F Song</name></author><author><name sortKey="Fux, R" uniqKey="Fux R">R Fux</name></author><author><name sortKey="Provacia, Lb" uniqKey="Provacia L">LB Provacia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Czub, M" uniqKey="Czub M">M Czub</name></author><author><name sortKey="Weingartl, H" uniqKey="Weingartl H">H Weingartl</name></author><author><name sortKey="Czub, S" uniqKey="Czub S">S Czub</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Van Kuppeveld, Fj" uniqKey="Van Kuppeveld F">FJ van Kuppeveld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Kou, Z" uniqKey="Kou Z">Z Kou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Kou, Z" uniqKey="Kou Z">Z Kou</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Geng, H" uniqKey="Geng H">H Geng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Zhong, Q" uniqKey="Zhong Q">Q Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kong, Wp" uniqKey="Kong W">WP Kong</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L Xu</name></author><author><name sortKey="Stadler, K" uniqKey="Stadler K">K Stadler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML DeDiego</name></author><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="See, Rh" uniqKey="See R">RH See</name></author><author><name sortKey="Zakhartchouk, An" uniqKey="Zakhartchouk A">AN Zakhartchouk</name></author><author><name sortKey="Petric, M" uniqKey="Petric M">M Petric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Becker, Mm" uniqKey="Becker M">MM Becker</name></author><author><name sortKey="Eckerle, Ld" uniqKey="Eckerle L">LD Eckerle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qu, D" uniqKey="Qu D">D Qu</name></author><author><name sortKey="Zheng, B" uniqKey="Zheng B">B Zheng</name></author><author><name sortKey="Yao, X" uniqKey="Yao X">X Yao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Netland, J" uniqKey="Netland J">J Netland</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML DeDiego</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fett, C" uniqKey="Fett C">C Fett</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML DeDiego</name></author><author><name sortKey="Regla Nava, Ja" uniqKey="Regla Nava J">JA Regla-Nava</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Jh" uniqKey="Kim J">JH Kim</name></author><author><name sortKey="Jacob, J Dn" uniqKey="Jacob J">J. DN Jacob</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalil, Ia" uniqKey="Khalil I">IA Khalil</name></author><author><name sortKey="Kogure, K" uniqKey="Kogure K">K Kogure</name></author><author><name sortKey="Akita, H" uniqKey="Akita H">H Akita</name></author><author><name sortKey="Harashima, H" uniqKey="Harashima H">H Harashima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satkauskas, S" uniqKey="Satkauskas S">S Šatkauskas</name></author><author><name sortKey="Bureau, Mf" uniqKey="Bureau M">MF Bureau</name></author><author><name sortKey="Mahfoudi, A" uniqKey="Mahfoudi A">A Mahfoudi</name></author><author><name sortKey="Mir, Lm" uniqKey="Mir L">LM Mir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shamlou, Pa" uniqKey="Shamlou P">PA Shamlou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prather, Kj" uniqKey="Prather K">KJ Prather</name></author><author><name sortKey="Sagar, S" uniqKey="Sagar S">S Sagar</name></author><author><name sortKey="Murphy, J" uniqKey="Murphy J">J Murphy</name></author><author><name sortKey="Chartrain, M" uniqKey="Chartrain M">M Chartrain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoare, M" uniqKey="Hoare M">M Hoare</name></author><author><name sortKey="Levy, Ms" uniqKey="Levy M">MS Levy</name></author><author><name sortKey="Bracewell, Dg" uniqKey="Bracewell D">DG Bracewell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Zy" uniqKey="Yang Z">ZY Yang</name></author><author><name sortKey="Kong, Wp" uniqKey="Kong W">WP Kong</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, B" uniqKey="Zhao B">B Zhao</name></author><author><name sortKey="Jin, Ny" uniqKey="Jin N">NY Jin</name></author><author><name sortKey="Wang, Rl" uniqKey="Wang R">RL Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Sq" uniqKey="Shi S">SQ Shi</name></author><author><name sortKey="Peng, Jp" uniqKey="Peng J">JP Peng</name></author><author><name sortKey="Li, Yc" uniqKey="Li Y">YC Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name></author><author><name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name></author><author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Tsoi, Hw" uniqKey="Tsoi H">HW Tsoi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bisht, H" uniqKey="Bisht H">H Bisht</name></author><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name></author><author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bukreyev, A" uniqKey="Bukreyev A">A Bukreyev</name></author><author><name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name></author><author><name sortKey="Buchholz, Uj" uniqKey="Buchholz U">UJ Buchholz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, W" uniqKey="Gao W">W Gao</name></author><author><name sortKey="Tamin, A" uniqKey="Tamin A">A Tamin</name></author><author><name sortKey="Soloff, A" uniqKey="Soloff A">A Soloff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pichla Gollon, Sl" uniqKey="Pichla Gollon S">SL Pichla-Gollon</name></author><author><name sortKey="Lin, S W" uniqKey="Lin S">S-W Lin</name></author><author><name sortKey="Hensley, Se" uniqKey="Hensley S">SE Hensley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, G" uniqKey="Gao G">G Gao</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Dai, Z" uniqKey="Dai Z">Z Dai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weingartl, H" uniqKey="Weingartl H">H Weingartl</name></author><author><name sortKey="Czub, M" uniqKey="Czub M">M Czub</name></author><author><name sortKey="Czub, S" uniqKey="Czub S">S Czub</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Bai, B" uniqKey="Bai B">B Bai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Yv" uniqKey="Liu Y">YV Liu</name></author><author><name sortKey="Massare, Mj" uniqKey="Massare M">MJ Massare</name></author><author><name sortKey="Barnard, Dl" uniqKey="Barnard D">DL Barnard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lokugamage, Kg" uniqKey="Lokugamage K">KG Lokugamage</name></author><author><name sortKey="Yoshikawa Iwata, N" uniqKey="Yoshikawa Iwata N">N Yoshikawa-Iwata</name></author><author><name sortKey="Ito, N" uniqKey="Ito N">N Ito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ho, Y" uniqKey="Ho Y">Y Ho</name></author><author><name sortKey="Lin, Ph" uniqKey="Lin P">PH Lin</name></author><author><name sortKey="Liu, Cy" uniqKey="Liu C">CY Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sailaja, G" uniqKey="Sailaja G">G Sailaja</name></author><author><name sortKey="Skountzou, I" uniqKey="Skountzou I">I Skountzou</name></author><author><name sortKey="Quan, Fs" uniqKey="Quan F">FS Quan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Bz" uniqKey="Wang B">BZ Wang</name></author><author><name sortKey="Quan, Fs" uniqKey="Quan F">FS Quan</name></author><author><name sortKey="Kang, Sm" uniqKey="Kang S">SM Kang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agnihothram, S" uniqKey="Agnihothram S">S Agnihothram</name></author><author><name sortKey="Gopal, R" uniqKey="Gopal R">R Gopal</name></author><author><name sortKey="Yount, Bl" uniqKey="Yount B">BL Yount</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naz, Rk" uniqKey="Naz R">RK Naz</name></author><author><name sortKey="Dabir, P" uniqKey="Dabir P">P Dabir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reed, Sg" uniqKey="Reed S">SG Reed</name></author><author><name sortKey="Bertholet, S" uniqKey="Bertholet S">S Bertholet</name></author><author><name sortKey="Coler, Rn" uniqKey="Coler R">RN Coler</name></author><author><name sortKey="Friede, M" uniqKey="Friede M">M Friede</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marciani, Dj" uniqKey="Marciani D">DJ Marciani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, Sl" uniqKey="Lambert S">SL Lambert</name></author><author><name sortKey="Yang, Cf" uniqKey="Yang C">CF Yang</name></author><author><name sortKey="Liu, Z" uniqKey="Liu Z">Z Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Podda, A" uniqKey="Podda A">A Podda</name></author><author><name sortKey="Del Giudice, G Mf" uniqKey="Del Giudice G">G. MF Del Giudice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Radosevi, K" uniqKey="Radosevi K">K Radošević</name></author><author><name sortKey="Rodriguez, A" uniqKey="Rodriguez A">A Rodriguez</name></author><author><name sortKey="Mintardjo, R" uniqKey="Mintardjo R">R Mintardjo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baldwin, Sl" uniqKey="Baldwin S">SL Baldwin</name></author><author><name sortKey="Bertholet, S" uniqKey="Bertholet S">S Bertholet</name></author><author><name sortKey="Reese, Va" uniqKey="Reese V">VA Reese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filipazzi, P" uniqKey="Filipazzi P">P Filipazzi</name></author><author><name sortKey="Pilla, L" uniqKey="Pilla L">L Pilla</name></author><author><name sortKey="Mariani, L" uniqKey="Mariani L">L Mariani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mavroudis, D" uniqKey="Mavroudis D">D Mavroudis</name></author><author><name sortKey="Bolonakis, I" uniqKey="Bolonakis I">I Bolonakis</name></author><author><name sortKey="Cornet, S" uniqKey="Cornet S">S Cornet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Sun, S" uniqKey="Sun S">S Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Budimir, N" uniqKey="Budimir N">N Budimir</name></author><author><name sortKey="Haan, A" uniqKey="Haan A">A Haan</name></author><author><name sortKey="Meijerhof, T" uniqKey="Meijerhof T">T Meijerhof</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frenck, Rw" uniqKey="Frenck R">RW Frenck</name></author><author><name sortKey="Belshe, R" uniqKey="Belshe R">R Belshe</name></author><author><name sortKey="Brady, Rc" uniqKey="Brady R">RC Brady</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahman, F" uniqKey="Rahman F">F Rahman</name></author><author><name sortKey="Dahmen, A" uniqKey="Dahmen A">A Dahmen</name></author><author><name sortKey="Herzog Auff, S" uniqKey="Herzog Auff S">S Herzog‐Hauff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mooney, Aj" uniqKey="Mooney A">AJ Mooney</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name></author><author><name sortKey="Gabbard, Jd" uniqKey="Gabbard J">JD Gabbard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siu, Y" uniqKey="Siu Y">Y Siu</name></author><author><name sortKey="Teoh, K" uniqKey="Teoh K">K Teoh</name></author><author><name sortKey="Lo, J" uniqKey="Lo J">J Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kitabatake, M" uniqKey="Kitabatake M">M Kitabatake</name></author><author><name sortKey="Inoue, S" uniqKey="Inoue S">S Inoue</name></author><author><name sortKey="Yasui, F" uniqKey="Yasui F">F Yasui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takasuka, N" uniqKey="Takasuka N">N Takasuka</name></author><author><name sortKey="Fujii, H" uniqKey="Fujii H">H Fujii</name></author><author><name sortKey="Takahashi, Y" uniqKey="Takahashi Y">Y Takahashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khosrow Tayebati, S" uniqKey="Khosrow Tayebati S">S Khosrow Tayebati</name></author><author><name sortKey="Ejike Nwankwo, I" uniqKey="Ejike Nwankwo I">I Ejike Nwankwo</name></author><author><name sortKey="Amenta, F" uniqKey="Amenta F">F Amenta</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Liew, Fy" uniqKey="Liew F">FY Liew</name></author><author><name sortKey="Russell, Sm" uniqKey="Russell S">SM Russell</name></author><author><name sortKey="Appleyard, G" uniqKey="Appleyard G">G Appleyard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Schutten, M" uniqKey="Schutten M">M Schutten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martina, Be" uniqKey="Martina B">BE Martina</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name></author><author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name></author><author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Prescott, J" uniqKey="Prescott J">J Prescott</name></author><author><name sortKey="Baseler, L" uniqKey="Baseler L">L Baseler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y Yao</name></author><author><name sortKey="Bao, L" uniqKey="Bao L">L Bao</name></author><author><name sortKey="Deng, W" uniqKey="Deng W">W Deng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name></author><author><name sortKey="Matthews, Kl" uniqKey="Matthews K">KL Matthews</name></author><author><name sortKey="Goicochea, L" uniqKey="Goicochea L">L Goicochea</name></author><author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devitt, E" uniqKey="Devitt E">E Devitt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Li, K" uniqKey="Li K">K Li</name></author><author><name sortKey="Wohlford Lenane, C" uniqKey="Wohlford Lenane C">C Wohlford-Lenane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reardon, S" uniqKey="Reardon S">S Reardon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K Narayanan</name></author><author><name sortKey="Maeda, A" uniqKey="Maeda A">A Maeda</name></author><author><name sortKey="Maeda, J" uniqKey="Maeda J">J Maeda</name></author><author><name sortKey="Makino, S" uniqKey="Makino S">S Makino</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Expert Rev Vaccines</journal-id><journal-id journal-id-type="iso-abbrev">Expert Rev Vaccines</journal-id><journal-id journal-id-type="publisher-id">IERV</journal-id><journal-id journal-id-type="publisher-id">ierv20</journal-id><journal-title-group><journal-title>Expert Review of Vaccines</journal-title></journal-title-group><issn pub-type="ppub">1476-0584</issn><issn pub-type="epub">1744-8395</issn><publisher><publisher-name>Taylor & Francis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24766432</article-id><article-id pub-id-type="pmc">4241375</article-id><article-id pub-id-type="publisher-id">912134</article-id><article-id pub-id-type="doi">10.1586/14760584.2014.912134</article-id><article-categories><subj-group subj-group-type="heading"><subject>Reviews</subject></subj-group></article-categories><title-group><article-title>Current advancements and potential strategies in the development of MERS-CoV vaccines</article-title><alt-title alt-title-type="running-title">Vaccine for MERS</alt-title><alt-title alt-title-type="running-authors">Zhang, Jiang & Du</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Naru</given-names></name><xref ref-type="aff" rid="AFF0001"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Shibo</given-names></name><xref ref-type="corresp" rid="AN0001"></xref><xref ref-type="aff" rid="AFF0001"><sup>a</sup></xref><xref ref-type="aff" rid="AFF0002"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Du</surname><given-names>Lanying</given-names></name><xref ref-type="corresp" rid="AN0001"></xref><xref ref-type="aff" rid="AFF0001"><sup>a</sup></xref></contrib><aff id="AFF0001"><label>a</label><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution><addr-line>New York, NY,</addr-line><country>USA</country></aff><aff id="AFF0002"><label>b</label><institution>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University,</institution><addr-line>Shanghai,</addr-line><country>China</country></aff></contrib-group><author-notes><corresp id="AN0001">*Authors for Correspondence: <phone>+1 212 570 3058; +1 212 570 3459</phone><email xlink:href="sjiang@nybloodcenter.org">sjiang@nybloodcenter.org</email>; <email xlink:href="ldu@nybloodcenter.org">ldu@nybloodcenter.org</email></corresp></author-notes><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>26</day><month>4</month><year>2014</year></pub-date><volume>13</volume><issue>6</issue><fpage seq="7">761</fpage><lpage>774</lpage><permissions><copyright-statement>© Informa UK, Ltd.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Informa UK, Ltd.</copyright-holder><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="IERV_13_912134.pdf"></self-uri><abstract><p>Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the <italic>in vivo</italic> efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords:</title><kwd>adjuvants</kwd><kwd>administration routes</kwd><kwd>coronavirus</kwd><kwd>MERS-CoV</kwd><kwd>Middle East respiratory syndrome</kwd><kwd>receptor-binding domain</kwd><kwd>spike protein</kwd><kwd>subunit vaccines</kwd><kwd>vaccines</kwd></kwd-group><counts><fig-count count="4"></fig-count><table-count count="2"></table-count><ref-count count="128"></ref-count><page-count count="14"></page-count></counts></article-meta></front><body><p>A novel β-coronavirus (β-CoV) named Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in humans in the Middle East in June 2012. The virus was isolated from a 60-year-old Saudi man who was diagnosed with progressive community-acquired pneumonia and subsequent acute renal failure with a fatal outcome <xref rid="CIT0001">[1]</xref>. Increasing numbers of cases have resulted from MERS-CoV infection as shown in <xref rid="F0001">Figure 1</xref><xref rid="CIT0002">[2]</xref>. As of 26 March 2014, a total of 200 human MERS-CoV infections with 85 deaths had been reported in the Middle East, North Africa and several European countries by WHO <xref rid="CIT0002">[2]</xref>.</p><fig fig-type="figure" id="F0001" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-F0001</object-id><label>Figure 1.</label><caption><p><bold>Laboratory confirmed cases of human infection with MERS-coronavirus.</bold> The black columns indicate the total laboratory confirmed human cases infected with MERS-CoV, while the gray columns demonstrate the total deaths caused by MERS-CoV infection from September 2012 to the indicated date.</p></caption><graphic content-type="black-white" xlink:href="IERV_A_912134_F0001_B"></graphic><p><fn id="FN0001"><p>MERS-CoV: MERS-coronavirus.</p></fn></p></fig><p>While many animals are considered reservoirs for CoVs, the origin of MERS-CoV and mode of disease transmission still remain unknown. Based on a sequence fragment identical to MERS-CoV found in a <italic>Taphozous perforates</italic> bat captured in Saudi Arabia, it has been inferred that bats are the most likely reservoir for MERS-CoV <xref rid="CIT0003">[3]</xref>. The identification of MERS-CoV in dromedary camels and the detection of neutralizing antibodies in the sera of these animals suggest that camels could be the intermediate host of MERS-CoV <xref rid="CIT0004 CIT0005">[4,5]</xref>. It is thus suspected that MERS-CoV emerged as interspecies transmission from bats to other animals, such as camels, and then to humans <xref rid="CIT0006">[6]</xref>.</p><p>Several family clusters with MERS-CoV infection have been reported <xref rid="CIT0007 CIT0008">[7,8]</xref>, suggesting human-to-human transmission of the disease. Most people who were infected with MERS-CoV developed severe acute respiratory illness with symptoms like fever, cough and shortness of breath. The virus has an estimated incubation period of 12 days <xref rid="CIT0009">[9]</xref>. The transmissibility of MERS-CoV between humans is currently less efficient than that of severe acute respiratory syndrome CoV (SARS-CoV), which emerged in Guangdong Province in China in 2002 and re-emerged in 2004, with over 8000 cases and more than 700 deaths in 29 countries throughout the world <xref rid="CIT0010">[10]</xref>. Nonetheless, the mortality rate for MERS (∼43%) is much higher than that for SARS (∼10%) <xref rid="CIT0011">[11]</xref>. It has been reported that MERS-CoV, but not SARS-CoV, could replicate in cell lines from four major chiropteran families, implying the ability of MERS-CoV in crossing species barrier between humans and bats <xref rid="CIT0012">[12]</xref>. With increased human cases and high mortality rate, MERS-CoV infection has raised serious global concerns, although it is still too early to implicate any impending pandemic. Vaccination is considered one of the most effective strategies to prevent virus infection. Thus, development of effective vaccines is essential to fight against this infectious disease.</p><sec id="S0002"><title>CoV classification & MERS-CoV characterization</title><p>As proposed by the Coronavirus Study Group of the International Committee for Taxonomy of Viruses (ICTV), three groups, 1, 2 and 3, of the Coronaviridae family have been commonly accepted as α-CoV, β-CoV and γ-CoV, respectively, where the genus β-CoV consists of four lineages, namely, A, B, C and D <xref rid="CIT0013">[13]</xref>. A novel genus, δ-CoV, including HKU11, HKU12 and HKU13 identified in birds in 2005, was added in the CoV genera <xref rid="CIT0013">[13]</xref>.</p><p>Unlike any other previously identified CoVs, such as α-CoV NL63, which was first reported in 2004 <xref rid="CIT0014">[14]</xref>, as well as β-CoV HKU1, which was first discovered in Hong Kong in 2005 <xref rid="CIT0015 CIT0016">[15,16]</xref> and SARS-CoV, which caused a worldwide outbreak in 2003 <xref rid="CIT0017">[17]</xref>, MERS-CoV belongs to lineage C of β-CoV, and is the first known lineage C β-CoV associated with human infections <xref rid="CIT0018">[18]</xref>. Phylogenetically, MERS-CoV is closely related to bat CoVs HKU4 and HKU5 <xref rid="CIT0019 CIT0020 CIT0021">[19–21]</xref>.</p><p>MERS-CoV is a positive-sense, single-stranded RNA virus. Its genome is about 30 kilobase (kb) pairs in length, consisting of 11 functional open reading frames (ORFs) <xref rid="F0002">(Figure 2 &</xref><xref rid="T0001">Table 1)</xref>. The viral genome encodes five unique proteins, known as accessory proteins (3, 4a, 4b, 5, 8b), which serve different functions with no known homologs to any other CoV proteins. Accessory protein 4a, for example, was recently proven to block the production of host interferon (IFN) <xref rid="CIT0022">[22]</xref>. Although these accessory proteins are not essential for virus replication, recent studies by reverse genetics demonstrated that the absence of the genes encoding these proteins as a group may attenuate viral titers <xref rid="CIT0023">[23]</xref>. Additionally, the genome of MERS-CoV encodes six proteins, which are homologous to those of the known CoVs, including two replicase proteins, ORFs 1a and 1b and four major structural proteins, such as spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins <xref rid="F0002">(Figure 2)</xref><xref rid="CIT0011">[11]</xref>. The E protein is a transmembrane protein forming an ion channel on the viral surface. The CoV N protein plays an important role in encapsidating the genomic RNA and interacting with the M protein and other N molecules <xref rid="CIT0024">[24]</xref>.</p><fig fig-type="figure" id="F0002" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-F0002</object-id><label>Figure 2.</label><caption><p><bold>Genomic and schematic diagram of MERS-coronavirus structure.</bold><bold>(A)</bold> MERS-CoV genomic structure. Viral genes, including ORF 1a, ORF 1b, S, 3, 4a, 4b, 5, E, M, 8b and N (GenBank accession number: JX869059) and their respective lengths, are indicated by rectangular boxes in the scheme. <bold>(B)</bold> Schematic diagram of MERS-CoV structure. MERS-CoV contains four structural proteins. The S protein is a type I transmembrane glycoprotein displayed on the surface of viral membrane as an oligomer. The E protein is also a transmembrane protein that forms an ion channel on the viral surface. The N protein plays an important role in encapsidating the genomic RNA and interacting with the membrane M protein and other N molecules.</p></caption><graphic content-type="black-white" xlink:href="IERV_A_912134_F0002_B"></graphic><p><fn id="FN0002"><p>E: Envelope; M: Membrane; N: Nucleocapsid; MERS-CoV: MERS-coronavirus; S: Spike.</p></fn></p></fig><table-wrap id="T0001" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-T0001</object-id><label>Table 1.</label><caption><p><bold>MERS-coronavirus RNA genome and protein coding assignments.</bold></p></caption><pmc-comment>OASIS TABLE HERE</pmc-comment>
<table frame="hsides" rules="groups"><colgroup><col width="1*" align="left"></col><col width="1*" align="left"></col><col width="1*" align="left"></col><col width="1*" align="left"></col></colgroup><thead valign="top"><tr><th align="left"><bold>Gene</bold></th><th align="left"><bold>Encoded polypeptides</bold></th><th align="left"><bold>Length (nucleotides)</bold></th><th align="left"><bold>Function</bold></th></tr></thead><tbody valign="top"><tr><td align="left">1</td><td align="left">1a</td><td align="left">13,176</td><td align="left">Not known</td></tr><tr><td align="left">2</td><td align="left">1b</td><td align="left">8061</td><td align="left">Not known</td></tr><tr><td align="left">3</td><td align="left">S</td><td align="left">4062</td><td align="left">Mediates receptor binding and membrane fusion <xref rid="CIT0043">[43]</xref></td></tr><tr><td align="left">4</td><td align="left">N</td><td align="left">1242</td><td align="left">Associates with RNA genome and interacts with C-terminal domain of M protein <xref rid="CIT0109">[109]</xref></td></tr><tr><td align="left">5</td><td align="left">4b</td><td align="left">741</td><td align="left">Blocks host interferon production <xref rid="CIT0022">[22]</xref></td></tr><tr><td align="left">6</td><td align="left">5</td><td align="left">675</td><td align="left">Not known</td></tr><tr><td align="left">7</td><td align="left">M</td><td align="left">660</td><td align="left">Incorporates viral components into virions and interacts with the N protein in infected cells <xref rid="CIT0128">[128]</xref></td></tr><tr><td align="left">8</td><td align="left">8b</td><td align="left">339</td><td align="left">Not known</td></tr><tr><td align="left">9</td><td align="left">4a</td><td align="left">330</td><td align="left">Not known</td></tr><tr><td align="left">10</td><td align="left">3</td><td align="left">312</td><td align="left">Not known</td></tr><tr><td align="left">11</td><td align="left">E</td><td align="left">249</td><td align="left">Ion channel activity</td></tr></tbody></table></table-wrap><p>The S protein of CoVs is a type I transmembrane glycoprotein displayed as an oligomer on the surface of the viral membrane. The precursor S protein contains a cleavage site at which the protein could be cleaved into two non-covalently associated subunits: the distal subunit S1 and the membrane-anchored subunit S2 <xref rid="CIT0025">[25]</xref>. The S1 subunit contains the cellular receptor-binding domain (RBD) <xref rid="CIT0026">[26]</xref>, while the S2 subunit contains a putative fusion peptide, transmembrane domain and two heptad repeat regions: the heptad repeat 1 and 2 (HR1 and HR2) <xref rid="F0003">(Figure 3)</xref><xref rid="CIT0027">[27]</xref>. <xref rid="F0003">Figure 3A</xref> lists the representative structures of S proteins of α- and β-CoV NL63-CoV, mouse hepatitis CoV (MHV-CoV) and SARS-CoV <xref rid="CIT0028 CIT0029 CIT0030">[28–30]</xref>, with the RBDs of these CoV S proteins consisting of respective core and receptor-binding subdomains. For example, the receptor-binding motif of SARS-CoV contains residues from 424 to 494, which form a long extended loop with two short antiparallel β-sheets and one disulfide bond between C467 and C474 <xref rid="CIT0031">[31]</xref>.</p><fig fig-type="figure" id="F0003" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-F0003</object-id><label>Figure 3.</label><caption><p><bold>Schematic diagrams of spike protein structures of representative coronaviruses.</bold> Schematic diagrams of the structures of S proteins of the previously identified coronaviruses NL63-CoV, MHV-CoV, SARS-CoV <bold>(A)</bold>, and the newly emerged coronavirus MERS-CoV <bold>(B)</bold> are indicated. The S proteins contain S1 and S2 subunits, respectively, with RBDs located in the S1 region. RBMs are functional regions within RBDs for receptor recognition. Other functional domains, such as fusion peptide, HR1, HR2, transmembrane and cytoplasmic tail, contain variant lengths within different coronaviruses.</p></caption><graphic content-type="black-white" xlink:href="IERV_A_912134_F0003_B"></graphic><p><fn id="FN0003"><p>MERS-CoV: MERS-coronavirus; MHV-CoV: Mouse hepatitis-CoV; RBD: Receptor-binding domain; RBM: Receptor-binding motif; S: Spike; SARS-CoV: Severe acute respiratory syndrome coronavirus.</p></fn></p></fig><p>Similar to the S proteins of other CoVs, the S protein of MERS-CoV also contains S1 and S2 subunits, with S1 being responsible for receptor binding and S2 for membrane fusion <xref rid="CIT0032">[32]</xref>. Unlike CoVs SARS-CoV and NL63-CoV, which use human angiotensin-converting enzyme 2 as their receptors <xref rid="CIT0033 CIT0034">[33,34]</xref>, MERS-CoV utilizes human dipeptidyl peptidase 4 (DPP4, also known as CD26) as its cellular receptor. DPP4 is expressed on primary bronchiolar epithelial cells and regulates the activity of hormones and chemokines through proteolytic cleavage <xref rid="CIT0012 CIT0035">[12,35]</xref>. Recent studies have solved the crystal structures of MERS-CoV S protein alone, or complexed with its receptor DPP4, and mapped the RBD of MERS-CoV to the residues covering 367–588 or 367–606, respectively <xref rid="CIT0032 CIT0036 CIT0037">[32,36,37]</xref>. According to the crystal structures, the RBD of MERS-CoV also contains the core and receptor-binding subdomains, with the receptor-binding motif consisting of 84 amino acids (from V484 to L567) that form a four-stranded antiparallel β-sheet <xref rid="F0003">(Figure 3B)</xref><xref rid="CIT0032 CIT0036">[32,36]</xref>. Similar to other CoVs, the HR1 and HR2 of MERS-CoV form a 6-helix bundle believed to drive virion-cell membrane fusion, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves <xref rid="CIT0023 CIT0038 CIT0039">[23,38,39]</xref>. <xref rid="F0004">Figure 4</xref> describes the crystal structures of SARS-CoV and MERS-CoV RBD complexed with their respective receptors, and the major neutralizing epitopes on SARS-CoV RBD for the neutralizing monoclonal antibody against SARS-CoV <xref rid="CIT0036 CIT0040 CIT0041 CIT0042">[36,40–42]</xref>. Understanding of these neutralizing epitopes in RBD of SARS-CoV will provide useful guidance for the identification of the neutralizing epitopes in MERS-CoV RBD and, hence designing RBD-based, neutralizing epitope-dependent vaccines against MERS-CoV.</p><fig fig-type="figure" id="F0004" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-F0004</object-id><label>Figure 4.</label><caption><p><bold>Crystal structures of SARS-CoV and MERS-CoV RBD and neutralizing epitopes on SARS-CoV RBD.</bold><bold>(A)</bold> Crystal structure of SARS-CoV RBD complexed with its receptor ACE2 (blue) (PDB ID: 2AJF) <xref rid="CIT0031">[31]</xref>. <bold>(B)</bold> Neutralizing epitope for mAb m396 Fab on SARS-CoV RBD (PDB ID: 2DD8) <xref rid="CIT0041">[41]</xref>. SARS-CoV RBD is in black with RBM region in yellow. <bold>(C)</bold> Neutralizing epitope for mAb F26G19 Fab on SARS-CoV RBD (PDB ID: 3BGF) <xref rid="CIT0040">[40]</xref>. <bold>(D)</bold> Neutralizing epitope for mAb 80R scFv on SARS-CoV RBD (PDB ID: 2GHW) <xref rid="CIT0042">[42]</xref>. <bold>(E)</bold> Crystal structure of MERS-CoV RBD. The RBM is in yellow. (PDB ID: 4KQZ) <xref rid="CIT0036">[36]</xref>. <bold>(F)</bold> Crystal structure of MERS-CoV RBD (black) complexed with its receptor human DPP4 (blue) (PDB ID: 4KR0) <xref rid="CIT0037">[37]</xref>.</p></caption><graphic content-type="black-white" xlink:href="IERV_A_912134_F0004_B"></graphic><p><fn id="FN0004"><p>ACE2: Angiotensin-converting enzyme 2; MERS-CoV: MERS-coronavirus; RBD: Receptor-binding domain; RBM: Receptor-binding motif; SARS-CoV: Severe acute respiratory syndrome coronavirus.</p></fn></p></fig><p>Previous reviews on SARS have summarized the approaches for the development of effective CoV vaccines, pointed out the importance of SARS-CoV S protein as a target for vaccine and therapeutic development and outlined a roadmap for the product development of a SARS-CoV RBD protein-based subunit vaccine with manufacturing for future clinical testing <xref rid="CIT0043 CIT0044 CIT0045 CIT0046">[43–46]</xref>. In this review, we will briefly discuss current stages of MERS vaccine development, and provide potential strategies for developing MERS vaccines based on the experience from development of SARS vaccines, with the focus on subunit vaccines and how to improve the efficacy of MERS subunit vaccines. In addition, we also summarize current animal models for MERS-CoV and emphasize the importance for evaluation of efficacy of MERS vaccine candidates in effective animal models.</p></sec><sec id="S0003"><title>Current advancements on MERS vaccine development</title><p>No currently licensed MERS vaccines are available for use. However, researchers are working to develop potential vaccines, and recent successes in the engineering of a replication-competent, propagation-defective MERS-CoV using reverse genetics provide the possibility of developing attenuated viruses as MERS vaccine candidates <xref rid="CIT0047">[47]</xref>.</p><p>SARS studies have demonstrated that vaccines inducing strong neutralizing antibodies completely protected immunized subjects against SARS-CoV infection. Moreover, recovered patients infected with SARS-CoV could maintain potent and persistent RBD-specific antibody responses with neutralizing activity <xref rid="CIT0048">[48]</xref>, revealing the significance of neutralizing antibodies in the prevention of SARS. Like the case of SARS-CoV vaccines, although vaccines eliciting favorable cellular immune responses may play a role in the clearance of virus infection, vaccines inducing neutralizing antibodies will be sufficient for protection from MERS-CoV infection. Thus, the ability of eliciting neutralizing antibodies is expected to be one of the important criteria for evaluating the efficacy of MERS vaccines.</p><p>Previous studies of SARS-CoV have shown that the S protein, particularly the RBD, may induce highly potent neutralizing antibodies that protected vaccinated animals against SARS-CoV challenge <xref rid="CIT0043 CIT0049 CIT0050 CIT0051">[43,49–51]</xref>. It is thus expected that the S protein in MERS-CoV will also be important for the development of vaccines. Song <italic>et al</italic>. showed that vaccination with a recombinant-modified vaccinia virus Ankara (MVA) expressing the full-length S protein of MERS-CoV induced high levels of neutralizing antibodies in vaccinated mice <xref rid="CIT0052">[52]</xref>. However, Cao and colleagues have reported that although the MVA-based, full-length S protein-dependent SARS vaccine could induce neutralizing antibody responses in ferrets, it failed to protect the vaccinated animals from SARS-CoV challenge. Even worse, this vaccine was associated with enhanced inflammatory and immunopathological effects, resulting in serious liver damage in the vaccinated ferrets after viral challenge <xref rid="CIT0053">[53]</xref>. Therefore, caution should be taken when the full-length S protein of MERS-CoV is used as a vaccine antigen since the non-neutralizing epitopes in S protein may induce antibody-mediated disease enhancement (ADE) effects, as those elicited by the S protein of feline infectious peritonitis virus (FIPV, also a CoV) <xref rid="CIT0054">[54]</xref>.</p><p>Therefore, it is favorable to develop vaccines based on S protein fragments, particularly RBD, of MERS-CoV, and such strategy has been reported to be effective in the development of MERS vaccines. Studies have shown that neutralization against MERS-CoV infection could be elicited in vaccinated rabbits by a fragment containing residues 358–588 of MERS-CoV S protein <xref rid="CIT0055">[55]</xref>. The induction of neutralizing activity by a recombinant protein fragment containing residues 377–662 of MERS-CoV RBD has also been demonstrated. Particularly, a truncated 212-amino acid RBD fragment containing residues 377–588 (inside RBD: residues 367–606) of MERS-CoV S protein induced strong MERS-CoV S-specific antibodies in vaccinated mice, blocking the binding of MERS-CoV RBD to viral receptor DPP4 and effectively neutralizing MERS-CoV infection, thus providing promise for further development as an effective and safe MERS vaccine <xref rid="CIT0056 CIT0057">[56,57]</xref>.</p><p>In addition to the S protein, other MERS-CoV viral proteins might play a role in the development of MERS candidate vaccines. However, few studies have addressed this possibility, in particular because MERS has only recently emerged as a novel human disease, and vaccine development is a time-consuming process. A recent study reveals that structural and accessory proteins, such as M, ORF 4a, ORF 4b and ORF 5, of MERS-CoV may function as potent IFN antagonists <xref rid="CIT0058">[58]</xref>, with ORF 4a protein showing the greatest potential for counteracting the antiviral effects of IFN by inhibiting IFN production and IFN-sensitive response element signaling pathways. Therefore, these proteins may also serve as targets for developing MERS vaccines.</p></sec><sec id="S0004"><title>Potential strategies for developing MERS vaccines</title><sec id="S0004-S2001"><title>Possibility for developing MERS vaccines with various types</title><p>Traditionally, inactivated and live-attenuated virus vaccines have been the most commonly developed and used vaccine types against viral pathogens, including SARS-CoV. Other types of vaccines, such as those based on DNA, viral vectors, virus-like particles (VLPs) and recombinant proteins, have also been discussed in terms of their potential application as MERS vaccine candidates. Because only a few papers related to the MERS-CoV vaccine development have been published so far, the rest of the review will discuss the development of SARS-CoV vaccines, from which we can learn what the best strategy is for developing MERS-CoV vaccine and how to move it forward more efficiently. The main advantages and disadvantages of different strategies for CoV vaccine development are listed in <xref rid="T0002">Table 2</xref>.</p><table-wrap id="T0002" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1586/14760584.2014.912134-T0002</object-id><label>Table 2.</label><caption><p><bold>The potential strengths and weaknesses of different types of coronavirus vaccines.</bold></p></caption><pmc-comment>OASIS TABLE HERE</pmc-comment>
<table frame="hsides" rules="groups"><colgroup><col width="1*" align="left"></col><col width="1*" align="left"></col><col width="1*" align="left"></col><col width="1*" align="left"></col></colgroup><thead valign="top"><tr><th align="left"><bold>Vaccines</bold></th><th align="left"><bold>Advantages</bold></th><th align="left"><bold>Disadvantages</bold></th><th align="right"><bold>Ref.</bold></th></tr></thead><tbody valign="top"><tr><td align="left">Inactivated and live-attenuated virus vaccines</td><td align="left">Inducing potent immune responses and protection against virus challenge; rapid development</td><td align="left">Relatively unsafe (having potential of recovering virulence); being inappropriate for highly immunosuppressed individuals</td><td align="right"><xref rid="CIT0059 CIT0060 CIT0061 CIT0062 CIT0063 CIT0064">[59–64]</xref></td></tr><tr><td align="left">DNA vaccines</td><td align="left">Easier to design; safe, minimizing undesirable side effects; stable and inexpensive</td><td align="left">Generally inducing lower immune responses; repeated doses may cause toxicity</td><td align="right"><xref rid="CIT0067 CIT0070 CIT0071 CIT0072 CIT0076">[67,70–72,76]</xref></td></tr><tr><td align="left">Viral vector-based vaccines</td><td align="left">Eliciting stronger and specific cellular and humoral immune responses</td><td align="left">Possibly presenting pre-existing immunity in humans and causing harmful immune responses and inflammation</td><td align="right"><xref rid="CIT0052 CIT0083 CIT0084 CIT0085">[52,83–85]</xref></td></tr><tr><td align="left">VLPs</td><td align="left">Containing no infectious viruses; possibly being produced in a variety of expression systems; being able to elicit neutralizing antibody responses and protection</td><td align="left">Requiring specific antigen-unrelated components for VLP formation; possibly inducing relatively lower immune responses</td><td align="right"><xref rid="CIT0087 CIT0088">[87,88]</xref></td></tr><tr><td align="left">Subunit vaccines</td><td align="left">High safety profile because no infectious materials involved; consistent production; no side effects at infection sites; inducing immune responses with neutralizing activity and/or protection</td><td align="left">Not always cost-effective; relatively lower immunogenicity; requiring appropriate adjuvants</td><td align="right"><xref rid="CIT0043 CIT0050 CIT0051 CIT0056 CIT0057">[43,50,51,56,57]</xref></td></tr><tr><td align="left">• Full-length S protein-based</td><td align="left">Inducing humoral and cellular immune responses as well as protection</td><td align="left">Having potential to induce harmful immune responses or antibody-mediated disease enhancement effects by the non-neutralizing epitopes</td><td align="right"><xref rid="CIT0043 CIT0085">[43,85]</xref></td></tr><tr><td align="left">• Receptor-binding domain-based</td><td align="left">Eliciting potent neutralizing antibody responses, mucosal immune responses and protection</td><td align="left">Requiring suitable adjuvants and appropriate vaccination routes</td><td align="right"><xref rid="CIT0050 CIT0057 CIT0093">[50,57,93]</xref></td></tr></tbody></table><table-wrap-foot><fn><p>VLP: Virus-like particle.</p></fn></table-wrap-foot></table-wrap><sec id="S0004-S2001-S3001"><title>Inactivated and live-attenuated virus vaccines</title><p>The inactivated and live-attenuated SARS-CoV has been tested as vaccine candidates, some of which are proven to be effective to provide protective immunity against SARS-CoV infection <xref rid="CIT0059 CIT0060 CIT0061">[59–61]</xref>. It was previously reported that a β-propiolactone-inactivated SARS-CoV vaccine administered subcutaneously (s.c.) to mice was more effective in inhibiting virus replication in the murine respiratory tract than the adenovirus-based N and S vaccine given either intranasally (i.n.) or intramuscularly (i.m.) <xref rid="CIT0062">[62]</xref>. In addition, a live, impaired-fidelity SARS-CoV vaccine with engineered inactivation of exonuclease activity protects aged and immunocompromised mice against lethal virus challenge <xref rid="CIT0063">[63]</xref>. Apparently, both local and serum antibody responses can be induced in inactivated SARS-CoV vaccinated mice <xref rid="CIT0064">[64]</xref>. Like SARS-CoV, it might be possible to attenuate MERS-CoV by deleting the envelope E protein to diminish virus growth in tissue culture, while abrogating virulence in animals <xref rid="CIT0065 CIT0066">[65,66]</xref>, or by inactivating exonuclease activity. In spite of the possibility of inducing highly potent immune responses and protection, vaccine candidates based on the inactivated and live-attenuated MERS-CoV might have the potential of recovering virulence, raising safety concerns; as such, this vaccine type may be inappropriate for use by highly immunosuppressed individuals.</p></sec><sec id="S0004-S2001-S3002"><title>DNA vaccines</title><p>DNA vaccines consist of a plasmid DNA, which has been genetically engineered to produce immunological response to protect organisms against diseases. DNA is usually administered through two routes, i.m. delivery and bombardment of the skin using a gene gun <xref rid="CIT0067">[67]</xref>. Currently, two popular theories of DNA uptake are used, including non-specific phagocytosis or pinocytosis and antigen-specific receptor-mediated uptake <xref rid="CIT0068 CIT0069">[68,69]</xref>. Containing non-replicating and non-infectious components and only encoding the protein of interest, DNA vaccines are safe for use, minimizing undesirable side effects <xref rid="CIT0067">[67]</xref>. In addition, vaccines based on DNAs are easy to be scaled up by the fermentation technique <xref rid="CIT0070 CIT0071 CIT0072">[70–72]</xref> and are generally stable and inexpensive.</p><p>The efficacy of DNA-based vaccines against SARS-CoV infection has been widely reviewed. It is revealed that a DNA vaccine encoding SARS-CoV S protein induces neutralizing antibody as well as T-cell responses that protect vaccinated mice from SARS-CoV challenge <xref rid="CIT0073">[73]</xref>. In addition, IgG antibody and T-cell-mediated immune responses are induced by DNA vaccines encoding S1 of SARS-CoV <xref rid="CIT0074">[74]</xref>. Interestingly, expression of M protein of SARS-CoV can augment immune responses induced by NP protein of a SARS-CoV DNA vaccine <xref rid="CIT0075">[75]</xref>. Nevertheless, compared with other vaccine types, such as inactivated and live-attenuated virus vaccines, DNA-based vaccines usually have lower immunogenicity <xref rid="CIT0076">[76]</xref>, indicating the need to further improve their immune efficacy. Although it is possible to use similar strategies to develop DNA-based vaccines against MERS-CoV infection, suitable measures such as priming-boost strategy or combination of DNA vaccines with other vaccination types should be considered to improve the immunogenicity of DNA-based MERS vaccines <xref rid="CIT0077">[77]</xref>.</p></sec><sec id="S0004-S2001-S3003"><title>Viral vector-based vaccines</title><p>Viral vectors have been applied as an important delivery vehicle for developing candidate vaccines against SARS-CoV infection. Currently, reported viral vectors for SARS vaccines include MVA, vesicular stomatitis virus, rhabdovirus, adenovirus, adeno-associated virus and attenuated parainfluenza virus <xref rid="CIT0078 CIT0079 CIT0080">[78–80]</xref>. Previous reports have indicated the ability of an MVA-based vaccine expressing SARS-CoV S protein in the induction of neutralizing antibody with protection of vaccinated mice against SARS-CoV challenge <xref rid="CIT0078">[78]</xref>. In addition, a combination of adenoviral-based SARS vaccines encoding S1, M and NP protein, respectively, induced strong neutralizing antibodies and T-cell immune responses, protecting immunized monkeys from challenge of SARS-CoV <xref rid="CIT0080">[80]</xref>. The induction of sufficient cellular and humoral immune responses has also been demonstrated with neutralizing activity by an adeno-associated virus-based vaccine containing RBD of SARS-CoV in the protection of SARS-CoV challenge <xref rid="CIT0081 CIT0082">[81,82]</xref>.</p><p>The above approaches for developing viral vector-based SARS vaccines can be adopted for the development of MERS vaccines. Indeed, MERS-CoV S protein delivered by an MVA vector induces in the vaccinated mice antibody responses with neutralizing activity <xref rid="CIT0052">[52]</xref>, bringing some hopes for the development of viral vector-based vaccines to prevent MERS-CoV infection. However, it should be noted that viral vector-based vaccines do have some disadvantages. For example, some vectors, such as MVA or adenovirus, have pre-existing immunity, or cause harmful immune responses <xref rid="CIT0083 CIT0084">[83,84]</xref> and inflammation <xref rid="CIT0085">[85]</xref>. Thus, caution should be taken when developing MERS vaccines using viral vectors.</p></sec><sec id="S0004-S2001-S3004"><title>VLPs as vaccines</title><p>VLP-based vaccines have been developed as a new generation of non-egg-based, cell culture-derived vaccine candidates against virus infection, and thus have gained much more attention for their potential promise in developing effective and safe vaccines against SARS-CoV <xref rid="CIT0086">[86]</xref>. VLPs can be produced in several expression systems, such as mammalian cells (e.g., 293T, CHO), yeast, recombinant vaccinia virus and baculovirus expression systems <xref rid="CIT0087 CIT0088">[87,88]</xref>. It is worth noting that the minimal components essential for VLP formation and the immunogenicity induced by VLPs need to be considered. Although M and E proteins of SARS-CoV are sufficient for the efficient formation of VLPs <xref rid="CIT0089">[89]</xref>, the immunogenicity induced by VLPs without S protein might be greatly reduced. By comparison, chimeric VLPs carrying SARS-CoV S protein, and E, M and N proteins of MHV-CoV elicited high levels of SARS-CoV-specific neutralizing antibodies, protecting vaccinated mice from SARS-CoV challenge <xref rid="CIT0088">[88]</xref>.</p><p>The above findings on SARS-CoV VLPs may be applied to constructing VLPs for MERS-CoV. Compared with inactivated and live-attenuated virus vaccines, VLPs do not contain the infectious materials, making VLP technology a promising alternative for MERS vaccine development. However, the immunogenicity of VLPs is relatively lower than that of inactivated and live-attenuated virus vaccines. Several strategies may be explored to increase the immunogenicity of VLPs. For example, dendritic cell-stimulating molecules or Toll-like receptor 5 ligand flagellin can be genetically engineered for incorporation into MERS-CoV VLPs to increase immunogenicity and enhance protective efficacy against further heterosubtypic virus challenge <xref rid="CIT0090 CIT0091">[90,91]</xref>.</p></sec><sec id="S0004-S2001-S3005"><title>Subunit vaccines</title><p>Compared with other types of vaccines, subunit vaccines can claim several unique advantages. The most important characteristic of subunit vaccines is their safety in that the components only contain synthetic peptides or recombinant proteins expressing specific immunogenic fragments of a pathogen, without the involvement of infectious viruses. Additionally, this type of vaccine is less likely to induce side effects at the injection sites, and consistent production can be attained for subunit vaccines because of constant conditions and well-defined pathogenic fragments. The above features have made subunit vaccines an attractive vaccine candidate.</p><p>Like SARS-CoV S protein, the S protein of MERS-CoV is also considered an important target for development of subunit vaccines, because it is the main antigenic component responsible for inducing host immune responses. Since the S protein contains regions for receptor binding and membrane fusion, S protein-based vaccines are expected to induce antibodies to block virus binding and subsequent membrane fusion or neutralize viral infection <xref rid="CIT0043">[43]</xref>. However, the S protein of SARS-CoV also contains some non-neutralizing epitopes in the immmunopredominant domain <xref rid="CIT0092">[92]</xref>, which may induce harmful immune responses <xref rid="CIT0085">[85]</xref>. Therefore, it is essential to identify and exclude the epitopes in the S protein that may induce harmful or ADE responses from the S protein-based MERS-CoV vaccines.</p><p>Experience from developing RBD-based SARS subunit vaccines provides important guidance on the rational design of RBD protein-based MERS vaccines. Since the RBD of SARS-CoV contains multiple neutralizing epitopes, RBD-based SARS subunit vaccines covering these neutralizing epitopes are able to induce potent neutralizing antibodies completely preventing SARS-CoV challenge <xref rid="CIT0050 CIT0051">[50,51]</xref>. Similarly, it has been shown that the RBD of MERS-CoV induced strong neutralizing antibody responses against infection of MERS-CoV <xref rid="CIT0056 CIT0057">[56,57]</xref> and that the MERS-CoV RBD does, indeed, contain several important neutralizing epitopes <xref rid="CIT0093">[93]</xref>. Accordingly, further optimization of the RBD and development of optimized RBD-based MERS subunit vaccines containing multiple neutralizing epitopes would be desirable and feasible to improve the vaccine efficacy.</p><p>Both MERS-CoV and SARS-CoV RBDs consist of a core and a receptor-binding subdomain. They share a high degree of structural similarity in the core subdomains, but the receptor-binding subdomains are notably divergent <xref rid="CIT0032">[32]</xref>. Because of variation of the receptor-binding subdomain region within subgroups of the same CoV or across different CoV groups, it is advisable to rationally design MERS subunit vaccines using chimeric S protein containing several neutralizing epitopes from divergent subgroups. This approach will provide a strategic platform for the rational design of subunit vaccines against future emerging CoVs by focusing on the chimeric S protein containing neutralizing epitopes from multiple virus strains across different subgroups <xref rid="CIT0094">[94]</xref>.</p><p>To summarize, although the inactivated and live-attenuated virus and viral vector-based vaccines are able to induce strong immune responses, their tendency to recover virulence or cause harmful immune responses raises safety concerns for the development of MERS vaccines. While DNA-based vaccines have a high safety profile, they may be unable to induce highly potent immune response and protection in humans and might cause toxic effect at the injection sites with the repeated vaccinations. By comparison, development of recombinant RBD protein-based MERS subunit vaccines remains a high priority, due to a variety of advantages noted above.</p></sec></sec><sec id="S0004-S2002"><title>Potential strategies for improving the immunogenicity of MERS subunit vaccines</title><p>In spite of a number of merits, protein-based subunit vaccines might have relatively lower immunogenicity as compared with inactivated and live-attenuated vaccines <xref rid="CIT0095">[95]</xref>, necessitating continued improvement in the immunogenicity of subunit vaccines. Two possibilities are discussed as potential strategies to improve the immunogenicity of MERS vaccine candidates.</p><sec id="S0004-S2002-S3001"><title>Formulation of subunit vaccines with suitable adjuvants</title><p>To improve the immunogenicity of MERS candidate vaccines, adjuvants should be selected and formulated on the basis of their mechanisms of action. Normally, vaccines with limited immunogenicity require the addition of specific adjuvants to stimulate a protective and long-lasting immune response <xref rid="CIT0096 CIT0097 CIT0098">[96–98]</xref>. Although a variety of novel adjuvants are now emerging and being investigated, only a few have been approved for clinical use. Both aluminum salt-based adjuvants, usually called ‘Alum’ and MF59<sup>TM</sup> can induce antigen-specific humoral and CTL responses <xref rid="CIT0099 CIT0100">[99,100]</xref>; hence, they have the potential for use in MERS-CoV subunit vaccines. Another adjuvant named glucopyranosyl lipid A, a synthetic TLR4 agonist, was also shown to improve the immunogenicity of a protein-based vaccine candidate <xref rid="CIT0101">[101]</xref>. Other adjuvants, such as Montanide ISA51, which has been approved for human use in Europe <xref rid="CIT0102 CIT0103">[102,103]</xref>, is used in making MERS and influenza subunit vaccines, demonstrating a strong ability to promote the induction of highly potent immune responses of these candidate vaccines <xref rid="CIT0056 CIT0057 CIT0104">[56,57,104]</xref>. Furthermore, the combination of two adjuvants with distinct mechanisms of action is also feasible to improve the efficacy of designed MERS subunit vaccines. Since Alum alone cannot induce strong Th1 immune responses, it is thus applicable to combine Alum with other adjuvants with potential complementary effects in a hope to improve the efficacy induced by Alum-adjuvanted subunit vaccines. For example, combination of Alum plus glucopyranosyl lipid A will be applied to improve the efficacy of a SARS-CoV RBD protein-based subunit vaccine <xref rid="CIT0045">[45]</xref>. Therefore, similar strategies can be utilized in MERS-CoV subunit vaccines to improve their immunogenicity.</p></sec><sec id="S0004-S2002-S3002"><title>Selection of suitable administration routes</title><p>Several administration routes, including i.m., intradermal, s.c. and i.n. pathways, have been used for vaccine immunization in both experimental research and clinical use. The route of vaccine administration directly influences both the quality and quantity of vaccine-induced immunity <xref rid="CIT0105 CIT0106 CIT0107 CIT0108">[105–108]</xref>. Traditional parenteral administration routes, such as i.m., intradermal and s.c., have been shown to induce favorable immune responses and/or protection against SARS-CoV and MERS-CoV infections <xref rid="CIT0057 CIT0109 CIT0110 CIT0111">[57,109–111]</xref>. It is demonstrated that i.m. vaccination with RBD protein of SARS-CoV elicits long-term immune responses with neutralizing activity, protecting immunized mice from SARS-CoV challenge <xref rid="CIT0050">[50]</xref>. Additionally, potent neutralizing antibodies and protection against SARS-CoV infection are observed in the mice s.c. vaccinated with SARS-CoV RBD proteins, respectively, expressed in mammalian cell, insect cell and <italic>Escherichia coli</italic> expression systems <xref rid="CIT0049 CIT0112">[49,112]</xref>. Furthermore, strong neutralizing antibody responses are revealed in the mice s.c.-vaccinated MERS-CoV RBD proteins <xref rid="CIT0056">[56]</xref>.</p><p>In addition to inducing systemic immunity, the stimulation of local immunity at mucosal sites has become an important objective for vaccination. Although there are some unfavorable features from the i.n. route, such as the possibility of delivering antigens into the central nervous system <xref rid="CIT0113">[113]</xref>, as well as the unsuitability for children younger than 2 years and adults older than 50 years, especially those with chronic pulmonary diseases and immunosuppression <xref rid="CIT0114">[114]</xref>, the advantages of the i.n. route outweigh its disadvantages. Reports have indicated that i.n. vaccination effectively induced both local and systemic immune responses, especially mucosal IgA, against mucosal pathogens, cross-protecting vaccinated animals from infection by homologous and heterologous strains of influenza virus <xref rid="CIT0115">[115]</xref>, as well as providing long-term protection against SARS-CoV infection <xref rid="CIT0081">[81]</xref>. As an important mucosal pathogen infecting humans via the mucosal pathway <xref rid="CIT0009">[9]</xref>, MERS vaccines delivered via the mucosal route are anticipated to elicit effective mucosal immune responses, as represented by mucosal IgA. Intranasal immunization of a subunit candidate vaccine containing recombinant RBD protein fused with Fc of human IgG has been demonstrated to induce strong anti-RBD- and anti-S1-specific neutralizing antibody responses, particularly IgA mucosal immune responses, against infections from MERS-CoV <xref rid="CIT0093">[93]</xref>, providing a fundamental basis for developing effective MERS mucosal vaccines.</p><p>Therefore, selection of suitable vaccination routes, combined with antigen formulation with appropriate adjuvants, will play important guidance for developing MERS-CoV subunit vaccines and further evaluating their efficacy against MERS-CoV infection.</p></sec></sec></sec><sec id="S0005"><title>Animal models for MERS-CoV</title><p>Establishment of effective animal models is important for evaluating the efficacy of candidate vaccines against MERS-CoV. Unlike SARS-CoV, which can infect a variety of animals, including non-human primates, and small animal models such as ferrets, hamsters and mice <xref rid="CIT0076 CIT0078 CIT0116 CIT0117 CIT0118">[76,78,116–118]</xref>, the animal species that could be infected by MERS-CoV are very limited. It has been shown that MERS-CoV is unable to replicate in hamsters, ferrets and mice <xref rid="CIT0119 CIT0120 CIT0121 CIT0122">[119–122]</xref>, significantly restricting the efficacy evaluation of MERS vaccines in small animal models. Although rhesus macaques can be infected by MERS-CoV, with the infected animals showing clinical signs of disease and virus replication <xref rid="CIT0123 CIT0124">[123,124]</xref>, the high cost of non-human primate models would prevent the majority of researchers from using this animal model. Therefore, the development of effective small animal models for MERS-CoV infection is urgently needed <xref rid="CIT0125">[125]</xref>. It was recently reported that mice transduced with adenoviral vectors expressing MERS-CoV’s receptor DPP4 were susceptible to MERS-CoV infection, with the infected mice developing pneumonia and clinical disease accompanied by histopathological changes <xref rid="CIT0126">[126]</xref>. Nevertheless, a better transgenic mouse model with the gene encoding human DPP4 integrated into its genome has been developed by several laboratories <xref rid="CIT0127">[127]</xref>.</p></sec><sec id="S0006"><title>Conclusions</title><p>Based on the previous experience in developing SARS-CoV vaccines, current advancements and potential strategies in the development of MERS-CoV vaccines have been discussed in this review. Apart from inactivated and live-attenuated virus vaccines, DNA- and VLP-based vaccines, particularly subunit vaccines containing the RBD of MERS-CoV S protein, are critically important. Additionally, suitable adjuvant formulation and appropriate administration routes may need to be further considered to enhance the immunogenicity of the vaccine candidates. Furthermore, development of effective animal models for MERS-CoV infection is important for evaluating the efficacy of MERS-CoV candidate vaccines. Taken together, the strategies discussed above will have important implications for the development of effective MERS vaccines in the future.</p></sec><sec id="S0007"><title>Expert commentary</title><p>MERS-CoV, as a newly emerging CoV, has raised worldwide concerns based on its ability to cause increasing number of human infections with limited human-to-human transmission, making it particularly important to explore efficient and safe measures for the control of the disease. Among these, vaccination is considered one of the most effective strategies to prevent virus infection. Different from other structural proteins (E, M and N), S protein of MERS-CoV plays a key role in virus infection via S1 binding to viral receptor, followed by subsequent virus and cell membrane fusion via S2. DPP4 was identified to be the cellular receptor of MERS-CoV. Subsequently, the viral RBD was mapped by crystal structural analysis into residues 367–588 and 367–606 in the S1 subunit of S protein. The truncated RBD containing residues 377–588 induced the highest neutralizing antibody response against virus infection in vaccinated animals and thus demonstrating the importance for developing S-RBD-based vaccines against MERS-CoV. Compared with other vaccine types, subunit vaccines possess a higher safety profile, having the potential to elicit stronger immune responses, including neutralizing antibodies. Suitable choices in adjuvant formulation and immunization routes can further increase the efficacy of such subunit vaccines, highlighting the need to develop MERS-CoV subunit vaccines based on the RBD of viral S protein.</p></sec><sec id="S0008"><title>Five-year view</title><p>In the next 5 years, the development of an effective and safe subunit vaccine against MERS can be expected. In particular, the development of a subunit vaccine based on the RBD of MERS-CoV S protein has the greatest potential to contain multiple neutralizing epitopes capable of inducing highly potent immune responses, particularly neutralizing activity, against MERS-CoV infection. The establishment of effective small animal models for MERS infection will allow economical and practical detection of protective efficacy of designed vaccines against challenges from both single and multiple MERS-CoV strains potentially occurring in humans. The application of similar vaccine development strategies against other CoVs that might cause human diseases in the future is also anticipated.</p></sec></body><back><sec><title>Acknowledgements</title><p><italic>We thank Yang Yang at the Department of Pharmacology, University of Minnesota Medical School for the structural analysis of SARS-CoV and MERS-CoV RBDs.</italic></p></sec><sec><title>Financial and competing interests disclosure</title><p><italic>This study was supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (AI109094). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.</italic></p><p><italic>No writing assistance was utilized in the production of this manuscript.</italic></p></sec><sec id="S0009"><title></title><boxed-text id="B0001" position="float" orientation="portrait"><caption><p>Key issues</p></caption><list list-type="bullet"><list-item><p>First identified in humans in June 2012, Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), and is currently causing increased human infections with high mortality.</p></list-item><list-item><p>Belonging to lineage C of β-CoV, phylogenetically related to bat-HKU4 and bat-HKU5, MERS-CoV is the first known lineage C β-CoV associated with human infections.</p></list-item><list-item><p>Human dipeptidyl peptidase 4 is an identified receptor for MERS-CoV, and the receptor-binding domain (RBD) of MERS-CoV has been mapped by crystal structure to the residues covering 367–588 or 367–606, respectively.</p></list-item><list-item><p>A truncated RBD fragment containing a 212-amino acid (residues 377–588) of MERS-CoV S protein induced strong RBD-specific antibodies, blocking MERS-CoV RBD binding to viral receptor dipeptidyl peptidase 4 and effectively neutralizing MERS-CoV infection, providing promise for further development as a MERS candidate vaccine.</p></list-item><list-item><p>MERS-CoV S protein and RBD-based subunit vaccines that contain multiple neutralizing epitopes possess high efficacy to induce strong neutralizing antibody responses and protective immunity against MERS-CoV infection, representing a direction for future design of effective MERS vaccines.</p></list-item><list-item><p>Subunit vaccines formulated with suitable adjuvants and administered with appropriate routes have a high potential to enhance the immunogenicity of MERS candidate vaccines.</p></list-item></list></boxed-text></sec><ref-list><title>References</title><p>Papers of special note have been highlighted as:</p><p>• of interest</p><p>•• of considerable interest</p><ref id="CIT0001"><label>1.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zaki</surname><given-names>AM</given-names></name>, <name name-style="western"><surname>van Boheemen</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Bestebroer</surname><given-names>TM</given-names></name>, et al.</person-group><article-title>Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia</article-title>. <source>N Engl J Med</source><year>2012</year>;<volume>367</volume>(<issue>19</issue>):<fpage>1814</fpage>-<lpage>20</lpage><pub-id pub-id-type="pmid">23075143</pub-id></mixed-citation><note><label>••</label><p><bold>First report about the isolation of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in humans.</bold></p></note></ref><ref id="CIT0002"><label>2.</label><mixed-citation publication-type="web"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Middle East respiratory syndrome coronavirus</article-title>. <article-title>(MERS-CoV) - update</article-title>. <comment>Available from:</comment><ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/2014_03_26/en/">www.who.int/csr/don/2014_03_26/en/</ext-link><comment>[Last accessed 26 March 2014]</comment></mixed-citation></ref><ref id="CIT0003"><label>3.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Memish</surname><given-names>ZA</given-names></name>, <name name-style="western"><surname>Mishra</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Olival</surname><given-names>K</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus in bats, Saudi Arabia</article-title>. <source>Emerg Infect Dis</source><year>2013</year>;<volume>19</volume>(<issue>11</issue>):<fpage>1819</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">24206838</pub-id></mixed-citation></ref><ref id="CIT0004"><label>4.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Haagmans</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Al Dhahiry</surname><given-names>SH</given-names></name>, <name name-style="western"><surname>Reusken</surname><given-names>CB</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation</article-title>. <source>Lancet Infect Dis</source><year>2013</year>;<volume>14</volume>(<issue>2</issue>):<fpage>140</fpage>-<lpage>5</lpage><pub-id pub-id-type="pmid">24355866</pub-id></mixed-citation></ref><ref id="CIT0005"><label>5.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Reusken</surname><given-names>CB</given-names></name>, <name name-style="western"><surname>Haagmans</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Müller</surname><given-names>MA</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study</article-title>. <source>Lancet Infect Dis</source><year>2013</year>;<volume>13</volume>(<issue>10</issue>):<fpage>859</fpage>-<lpage>66</lpage><pub-id pub-id-type="pmid">23933067</pub-id></mixed-citation></ref><ref id="CIT0006"><label>6.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Balkhair</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Al Maamari</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Alawi</surname><given-names>FB</given-names></name></person-group><article-title>The struggle against MERS-CoV (the novel coronavirus)</article-title>. <source>Oman Med J</source><year>2013</year>;<volume>28</volume>(<issue>4</issue>):<fpage>226</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">23904912</pub-id></mixed-citation></ref><ref id="CIT0007"><label>7.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Memish</surname><given-names>ZA</given-names></name>, <name name-style="western"><surname>Zumla</surname><given-names>AI</given-names></name>, <name name-style="western"><surname>Al-Hakeem</surname><given-names>RF</given-names></name>, et al.</person-group><article-title>Family cluster of Middle East respiratory syndrome coronavirus infections</article-title>. <source>N Engl J Med</source><year>2013</year>;<volume>368</volume>:<fpage>2487</fpage>-<lpage>94</lpage><pub-id pub-id-type="pmid">23718156</pub-id></mixed-citation></ref><ref id="CIT0008"><label>8.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mailles</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Blanckaert</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Chaud</surname><given-names>P</given-names></name>, et al.</person-group><article-title>First cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013</article-title>. <source>Euro Surveill</source><year>2013</year>;<volume>18</volume>(<fpage>24):pii. 20502</fpage></mixed-citation></ref><ref id="CIT0009"><label>9.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Guery</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Poissy</surname><given-names>J</given-names></name>, <name name-style="western"><surname>el Mansouf</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission</article-title>. <source>Lancet</source><year>2013</year>;<volume>381</volume>(<issue>9885</issue>):<fpage>2265</fpage>-<lpage>72</lpage><pub-id pub-id-type="pmid">23727167</pub-id></mixed-citation></ref><ref id="CIT0010"><label>10.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Morens</surname><given-names>DM</given-names></name>, <name name-style="western"><surname>Folkers</surname><given-names>GK</given-names></name>, <name name-style="western"><surname>Fauci</surname><given-names>AS</given-names></name></person-group><article-title>The challenge of emerging and re-emerging infectious diseases</article-title>. <source>Nature</source><year>2004</year>;<volume>430</volume>(<issue>6996</issue>):<fpage>242</fpage>-<lpage>9</lpage><pub-id pub-id-type="pmid">15241422</pub-id></mixed-citation></ref><ref id="CIT0011"><label>11.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>McBride</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Fielding</surname><given-names>BC</given-names></name></person-group><article-title>The role of Severe Acute Respiratory Syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis</article-title>. <source>Viruses</source><year>2012</year>;<volume>4</volume>(<issue>11</issue>):<fpage>2902</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">23202509</pub-id></mixed-citation></ref><ref id="CIT0012"><label>12.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Müller</surname><given-names>MA</given-names></name>, <name name-style="western"><surname>Raj</surname><given-names>VS</given-names></name>, <name name-style="western"><surname>Muth</surname><given-names>D</given-names></name>, et al.</person-group><article-title>Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines</article-title>. <source>MBio</source><year>2012</year>;<volume>3</volume>:<issue>6</issue></mixed-citation></ref><ref id="CIT0013"><label>13.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Lam</surname><given-names>CS</given-names></name>, et al.</person-group><article-title>Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus</article-title>. <source>J Virol</source><year>2012</year>;<volume>86</volume>(<issue>7</issue>):<fpage>3995</fpage>-<lpage>4008</lpage><pub-id pub-id-type="pmid">22278237</pub-id></mixed-citation></ref><ref id="CIT0014"><label>14.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Fouchier</surname><given-names>RA</given-names></name>, <name name-style="western"><surname>Hartwig</surname><given-names>NG</given-names></name>, <name name-style="western"><surname>Bestebroer</surname><given-names>TM</given-names></name>, et al.</person-group><article-title>A previously undescribed coronavirus associated with respiratory disease in humans</article-title>. <source>Proc Natl Acad Sci USA</source><year>2004</year>;<volume>101</volume>(<issue>16</issue>):<fpage>6212</fpage>-<lpage>16</lpage><pub-id pub-id-type="pmid">15073334</pub-id></mixed-citation></ref><ref id="CIT0015"><label>15.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Yip</surname><given-names>CC</given-names></name>, et al.</person-group><article-title>Coronavirus HKU1 and other coronavirus infections in Hong Kong</article-title>. <source>J Clin Microbiol</source><year>2006</year>;<volume>44</volume>(<issue>6</issue>):<fpage>2063</fpage>-<lpage>71</lpage><pub-id pub-id-type="pmid">16757599</pub-id></mixed-citation></ref><ref id="CIT0016"><label>16.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Chu</surname><given-names>CM</given-names></name>, et al.</person-group><article-title>Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia</article-title>. <source>J Virol</source><year>2005</year>;<volume>79</volume>(<issue>2</issue>):<fpage>884</fpage>-<lpage>95</lpage><pub-id pub-id-type="pmid">15613317</pub-id></mixed-citation></ref><ref id="CIT0017"><label>17.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhong</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Zheng</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003</article-title>. <source>Lancet</source><year>2003</year>;<volume>362</volume>(<issue>9393</issue>):<fpage>1353</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">14585636</pub-id></mixed-citation></ref><ref id="CIT0018"><label>18.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chan</surname><given-names>JF</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name></person-group><article-title>The emerging novel Middle East respiratory syndrome coronavirus: the “knowns” and “unknowns”</article-title>. <source>J Formos Med Assoc</source><year>2013</year>;<volume>112</volume>(<issue>7</issue>):<fpage>372</fpage>-<lpage>81</lpage><pub-id pub-id-type="pmid">23883791</pub-id></mixed-citation></ref><ref id="CIT0019"><label>19.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name>, et al.</person-group><article-title>Molecular diversity of coronaviruses in bats</article-title>. <source>Virology</source><year>2006</year>;<volume>351</volume>(<issue>1</issue>):<fpage>180</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">16647731</pub-id></mixed-citation></ref><ref id="CIT0020"><label>20.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, et al.</person-group><article-title>Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features</article-title>. <source>J Virol</source><year>2007</year>;<volume>81</volume>(<issue>4</issue>):<fpage>1574</fpage>-<lpage>85</lpage><pub-id pub-id-type="pmid">17121802</pub-id></mixed-citation></ref><ref id="CIT0021"><label>21.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name>, et al.</person-group><article-title>Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats</article-title>. <source>Proc Natl Acad Sci USA</source><year>2005</year>;<volume>102</volume>(<issue>39</issue>):<fpage>14040</fpage>-<lpage>5</lpage><pub-id pub-id-type="pmid">16169905</pub-id></mixed-citation></ref><ref id="CIT0022"><label>22.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Niemeyer</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Zillinger</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Muth</surname><given-names>D</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>22</issue>):<fpage>12489</fpage>-<lpage>95</lpage><pub-id pub-id-type="pmid">24027320</pub-id></mixed-citation></ref><ref id="CIT0023"><label>23.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Scobey</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Yount</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Sims</surname><given-names>AC</given-names></name>, et al.</person-group><article-title>Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus</article-title>. <source>Proc Natl Acad Sci USA</source><year>2013</year>;<volume>110</volume>(<issue>40</issue>):<fpage>16157</fpage>-<lpage>62</lpage><pub-id pub-id-type="pmid">24043791</pub-id></mixed-citation></ref><ref id="CIT0024"><label>24.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hurst</surname><given-names>KR</given-names></name>, <name name-style="western"><surname>Ye</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Goebel</surname><given-names>SJ</given-names></name>, et al.</person-group><article-title>An interaction between the nucleocapsid protein and a component of the replicase-transcriptase complex is crucial for the infectivity of coronavirus genomic RNA</article-title>. <source>J Virol</source><year>2010</year>;<volume>84</volume>(<issue>19</issue>):<fpage>10276</fpage>-<lpage>88</lpage><pub-id pub-id-type="pmid">20660183</pub-id></mixed-citation></ref><ref id="CIT0025"><label>25.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Xu</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Lou</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core</article-title>. <source>J Biol Chem</source><year>2004</year>;<volume>279</volume>(<issue>47</issue>):<fpage>49414</fpage>-<lpage>19</lpage><pub-id pub-id-type="pmid">15345712</pub-id></mixed-citation></ref><ref id="CIT0026"><label>26.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bonavia</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Zelus</surname><given-names>BD</given-names></name>, <name name-style="western"><surname>Wentworth</surname><given-names>DE</given-names></name>, et al.</person-group><article-title>Identification of a receptor-binding domain of the spike glycoprotein of human coronavirus HCoV-229E</article-title>. <source>J Virol</source><year>2003</year>;<volume>77</volume>(<issue>4</issue>):<fpage>2530</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">12551991</pub-id></mixed-citation></ref><ref id="CIT0027"><label>27.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Taguchi</surname><given-names>F</given-names></name></person-group><article-title>The S2 subunit of the murine coronavirus spike protein is not involved in receptor binding</article-title>. <source>J Virol</source><year>1995</year>;<volume>69</volume>(<issue>11</issue>):<fpage>7260</fpage>-<lpage>3</lpage><pub-id pub-id-type="pmid">7474149</pub-id></mixed-citation></ref><ref id="CIT0028"><label>28.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wu</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Peng</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>F</given-names></name></person-group><article-title>Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor</article-title>. <source>Proc Natl Acad Sci USA</source><year>2009</year>;<volume>106</volume>(<issue>47</issue>):<fpage>19970</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">19901337</pub-id></mixed-citation></ref><ref id="CIT0029"><label>29.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Peng</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Sun</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Rajashankar</surname><given-names>KR</given-names></name>, et al.</person-group><article-title>Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor</article-title>. <source>Proc Natl Acad Sci USA</source><year>2011</year>;<volume>108</volume>(<issue>26</issue>):<fpage>10696</fpage>-<lpage>701</lpage><pub-id pub-id-type="pmid">21670291</pub-id></mixed-citation></ref><ref id="CIT0030"><label>30.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhu</surname><given-names>X</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>Q</given-names></name>, <name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Receptor-binding domain as a target for developing SARS vaccines</article-title>. <source>J Thorac Dis</source><year>2013</year>;<volume>5</volume>(<issue>Suppl 2</issue>):<fpage>S142</fpage><pub-id pub-id-type="pmid">23977435</pub-id></mixed-citation></ref><ref id="CIT0031"><label>31.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Li</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Farzan</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Harrison</surname><given-names>SC</given-names></name></person-group><article-title>Structure of SARS coronavirus spike receptor-binding domain complexed with receptor</article-title>. <source>Science</source><year>2005</year>;<volume>309</volume>(<issue>5742</issue>):<fpage>1864</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">16166518</pub-id></mixed-citation></ref><ref id="CIT0032"><label>32.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Shi</surname><given-names>X</given-names></name>, <name name-style="western"><surname>Jiang</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4</article-title>. <source>Cell Res</source><year>2013</year>;<volume>23</volume>(<issue>8</issue>):<fpage>986</fpage>-<lpage>93</lpage><pub-id pub-id-type="pmid">23835475</pub-id></mixed-citation><note><label>••</label><p><bold>Crystal structural analysis of MERS-CoV receptor-binding domain (RBD) complexed with dipeptidyl peptidase 4 (DPP4) receptor.</bold></p></note></ref><ref id="CIT0033"><label>33.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hofmann</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Pyrc</surname><given-names>K</given-names></name>, <name name-style="western"><surname>van der Hoek</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry</article-title>. <source>Proc Natl Acad Sci USA</source><year>2005</year>;<volume>102</volume>(<issue>22</issue>):<fpage>7988</fpage>-<lpage>93</lpage><pub-id pub-id-type="pmid">15897467</pub-id></mixed-citation></ref><ref id="CIT0034"><label>34.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Li</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Moore</surname><given-names>MJ</given-names></name>, <name name-style="western"><surname>Vasilieva</surname><given-names>N</given-names></name>, et al.</person-group><article-title>Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus</article-title>. <source>Nature</source><year>2003</year>;<volume>426</volume>(<issue>6965</issue>):<fpage>450</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">14647384</pub-id></mixed-citation></ref><ref id="CIT0035"><label>35.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Raj</surname><given-names>VS</given-names></name>, <name name-style="western"><surname>Mou</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Smits</surname><given-names>SL</given-names></name>, et al.</person-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title>. <source>Nature</source><year>2013</year>;<volume>495</volume>(<issue>7440</issue>):<fpage>251</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">23486063</pub-id></mixed-citation><note><label>••</label><p><bold>First report about the identification of DPP4 as MERS-CoV’s receptor.</bold></p></note></ref><ref id="CIT0036"><label>36.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chen</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Rajashankar</surname><given-names>KR</given-names></name>, <name name-style="western"><surname>Yang</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>19</issue>):<fpage>10777</fpage>-<lpage>83</lpage><pub-id pub-id-type="pmid">23903833</pub-id></mixed-citation><note><label>••</label><p><bold>Crystal structural analysis of MERS-CoV RBD.</bold></p></note></ref><ref id="CIT0037"><label>37.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lu</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Hu</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>Q</given-names></name>, et al.</person-group><article-title>Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26</article-title>. <source>Nature</source><year>2013</year>;<volume>500</volume>(<issue>7461</issue>):<fpage>227</fpage>-<lpage>31</lpage><pub-id pub-id-type="pmid">23831647</pub-id></mixed-citation><note><label>••</label><p><bold>First report about the crystal structural analysis of MERS-CoV RBD complexed with DPP4 receptor.</bold></p></note></ref><ref id="CIT0038"><label>38.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gao</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Lu</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Qi</surname><given-names>J</given-names></name>, et al.</person-group><article-title>Structure of the fusion core and inhibition of fusion by a heptad-repeat peptide derived from the S protein of MERS-CoV</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>24</issue>):<fpage>13134</fpage>-<lpage>40</lpage><pub-id pub-id-type="pmid">24067982</pub-id></mixed-citation></ref><ref id="CIT0039"><label>39.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lu</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>Q</given-names></name>, <name name-style="western"><surname>Zhu</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Structure-based discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) fusion inhibitor</article-title>. <source>Nat Commun</source><year>2014</year>;<volume>5</volume>:<fpage>3067</fpage><pub-id pub-id-type="pmid">24473083</pub-id></mixed-citation><note><label>••</label><p><bold>Description of the interaction between HR1 and HR2 domains in MERS-CoV spike proteins to form a 6-helix bundle core and mediate virion-cell membrane fusion as well as discovery of a potent peptide MERS-CoV fusion inhibitor.</bold></p></note></ref><ref id="CIT0040"><label>40.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Pak</surname><given-names>JE</given-names></name>, <name name-style="western"><surname>Sharon</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Satkunarajah</surname><given-names>M</given-names></name>, et al.</person-group><article-title>Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain</article-title>. <source>J Mol Biol</source><year>2009</year>;<volume>388</volume>(<issue>4</issue>):<fpage>815</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">19324051</pub-id></mixed-citation></ref><ref id="CIT0041"><label>41.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Prabakaran</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Gan</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Feng</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody</article-title>. <source>J Biol Chem</source><year>2006</year>;<volume>281</volume>(<issue>23</issue>):<fpage>15829</fpage>-<lpage>36</lpage><pub-id pub-id-type="pmid">16597622</pub-id></mixed-citation></ref><ref id="CIT0042"><label>42.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hwang</surname><given-names>WC</given-names></name>, <name name-style="western"><surname>Lin</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Santelli</surname><given-names>E</given-names></name>, et al.</person-group><article-title>Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody</article-title>. <source>J Biol Chem</source><year>2006</year>;<volume>281</volume>(<issue>45</issue>):<fpage>34610</fpage>-<lpage>16</lpage><pub-id pub-id-type="pmid">16954221</pub-id></mixed-citation></ref><ref id="CIT0043"><label>43.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>He</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Zhou</surname><given-names>Y</given-names></name>, et al.<name name-style="western"><surname>The spike protein of</surname><given-names>SARS-</given-names></name></person-group><article-title>CoV—a target for vaccine and therapeutic development</article-title>. <source>Nature Rev Microbiol</source><year>2009</year>;<volume>7</volume>(<issue>3</issue>):<fpage>226</fpage>-<lpage>36</lpage><pub-id pub-id-type="pmid">19198616</pub-id></mixed-citation></ref><ref id="CIT0044"><label>44.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Graham</surname><given-names>RL</given-names></name>, <name name-style="western"><surname>Donaldson</surname><given-names>EF</given-names></name>, <name name-style="western"><surname>Baric</surname><given-names>RS</given-names></name></person-group><article-title>A decade after SARS: strategies for controlling emerging coronaviruses</article-title>. <source>Nature Rev Microbiol</source><year>2013</year>;<volume>11</volume>(<issue>12</issue>):<fpage>836</fpage>-<lpage>48</lpage><pub-id pub-id-type="pmid">24217413</pub-id></mixed-citation></ref><ref id="CIT0045"><label>45.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Jiang</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Bottazzi</surname><given-names>ME</given-names></name>, <name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome</article-title>. <source>Expert Rev Vaccines</source><year>2012</year>;<volume>11</volume>(<issue>12</issue>):<fpage>1405</fpage>-<lpage>13</lpage><pub-id pub-id-type="pmid">23252385</pub-id></mixed-citation></ref><ref id="CIT0046"><label>46.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zakhartchouk</surname><given-names>AN</given-names></name>, <name name-style="western"><surname>Sharon</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Satkunarajah</surname><given-names>M</given-names></name>, et al.</person-group><article-title>Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: implications for a subunit vaccine</article-title>. <source>Vaccine</source><year>2007</year>;<volume>25</volume>(<issue>1</issue>):<fpage>136</fpage>-<lpage>43</lpage><pub-id pub-id-type="pmid">16919855</pub-id></mixed-citation></ref><ref id="CIT0047"><label>47.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Almazán</surname><given-names>F</given-names></name>, <name name-style="western"><surname>DeDiego</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Sola</surname><given-names>I</given-names></name>, et al.</person-group><article-title>Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate</article-title>. <source>mBio</source><year>2013</year>;<volume>4</volume>(<issue>5</issue>):<fpage>e00650</fpage>-<lpage>13</lpage><pub-id pub-id-type="pmid">24023385</pub-id></mixed-citation></ref><ref id="CIT0048"><label>48.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cao</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients</article-title>. <source>Virol J</source><year>2010</year>;<volume>7</volume>(<issue>1</issue>):<fpage>299</fpage><pub-id pub-id-type="pmid">21047436</pub-id></mixed-citation></ref><ref id="CIT0049"><label>49.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Chan</surname><given-names>C</given-names></name>, et al.</person-group><article-title>Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity</article-title>. <source>Virology</source><year>2009</year>;<volume>393</volume>(<issue>1</issue>):<fpage>144</fpage>-<lpage>50</lpage><pub-id pub-id-type="pmid">19683779</pub-id></mixed-citation></ref><ref id="CIT0050"><label>50.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>He</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model</article-title>. <source>Vaccine</source><year>2007</year>;<volume>25</volume>(<issue>15</issue>):<fpage>2832</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">17092615</pub-id></mixed-citation></ref><ref id="CIT0051"><label>51.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>He</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Lu</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Siddiqui</surname><given-names>P</given-names></name>, et al.</person-group><article-title>Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies</article-title>. <source>J Immunol</source><year>2005</year>;<volume>174</volume>(<issue>8</issue>):<fpage>4908</fpage>-<lpage>15</lpage><pub-id pub-id-type="pmid">15814718</pub-id></mixed-citation></ref><ref id="CIT0052"><label>52.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Song</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Fux</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Provacia</surname><given-names>LB</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>21</issue>):<fpage>11950</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">23986586</pub-id></mixed-citation><note><label>•</label><p><bold>A report about the induction of neutralizing antibody response in mice immunized with modified vaccinia virus Ankara expressing full-length MERS-CoV spike protein.</bold></p></note></ref><ref id="CIT0053"><label>53.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Czub</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Weingartl</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Czub</surname><given-names>S</given-names></name>, et al.</person-group><article-title>Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets</article-title>. <source>Vaccine</source><year>2005</year>;<volume>23</volume>(<issue>17</issue>):<fpage>2273</fpage>-<lpage>9</lpage><pub-id pub-id-type="pmid">15755610</pub-id></mixed-citation></ref><ref id="CIT0054"><label>54.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Olsen</surname><given-names>CW</given-names></name></person-group><article-title>A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination</article-title>. <source>Vet Microbiol</source><year>1993</year>;<volume>36</volume>(<issue>1</issue>):<fpage>1</fpage>-<lpage>37</lpage><pub-id pub-id-type="pmid">8236772</pub-id></mixed-citation></ref><ref id="CIT0055"><label>55.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mou</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Raj</surname><given-names>VS</given-names></name>, <name name-style="western"><surname>van Kuppeveld</surname><given-names>FJ</given-names></name>, et al.</person-group><article-title>The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>16</issue>):<fpage>9379</fpage>-<lpage>83</lpage><pub-id pub-id-type="pmid">23785207</pub-id></mixed-citation><note><label>•</label><p><bold>Description of the RBD in MERS-CoV spike (S) protein and its role in induction of neutralizing antibody response.</bold></p></note></ref><ref id="CIT0056"><label>56.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Kou</surname><given-names>Z</given-names></name>, et al.</person-group><article-title>Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>17</issue>):<fpage>9939</fpage>-<lpage>42</lpage><pub-id pub-id-type="pmid">23824801</pub-id></mixed-citation><note><label>•</label><p><bold>Description of the RBD in MERS-CoV S protein and its role in induction of neutralizing antibody response.</bold></p></note></ref><ref id="CIT0057"><label>57.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Kou</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Ma</surname><given-names>C</given-names></name>, et al.</person-group><article-title>A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines</article-title>. <source>PLoS One</source><year>2013</year>;<volume>8</volume>(<issue>12</issue>):<fpage>e81587</fpage><pub-id pub-id-type="pmid">24324708</pub-id></mixed-citation><note><label>••</label><p><bold>A report about a truncated RBD in MERS-CoV S protein as a therapeutic and vaccine target.</bold></p></note></ref><ref id="CIT0058"><label>58.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Zhang</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Geng</surname><given-names>H</given-names></name>, et al.</person-group><article-title>The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists</article-title>. <source>Protein Cell</source><year>2013</year>;<volume>4</volume>(<issue>12</issue>):<fpage>951</fpage>-<lpage>61</lpage><pub-id pub-id-type="pmid">24318862</pub-id></mixed-citation></ref><ref id="CIT0059"><label>59.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhou</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Zhong</surname><given-names>Q</given-names></name>, et al.</person-group><article-title>Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys</article-title>. <source>Vaccine</source><year>2005</year>;<volume>23</volume>(<issue>24</issue>):<fpage>3202</fpage>-<lpage>9</lpage><pub-id pub-id-type="pmid">15837221</pub-id></mixed-citation></ref><ref id="CIT0060"><label>60.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kong</surname><given-names>WP</given-names></name>, <name name-style="western"><surname>Xu</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Stadler</surname><given-names>K</given-names></name>, et al.</person-group><article-title>Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization</article-title>. <source>J Virol</source><year>2005</year>;<volume>79</volume>(<issue>22</issue>):<fpage>13915</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">16254327</pub-id></mixed-citation></ref><ref id="CIT0061"><label>61.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lamirande</surname><given-names>EW</given-names></name>, <name name-style="western"><surname>DeDiego</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Roberts</surname><given-names>A</given-names></name>, et al.</person-group><article-title>A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters</article-title>. <source>J Virol</source><year>2008</year>;<volume>82</volume>(<issue>15</issue>):<fpage>7721</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">18463152</pub-id></mixed-citation></ref><ref id="CIT0062"><label>62.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>See</surname><given-names>RH</given-names></name>, <name name-style="western"><surname>Zakhartchouk</surname><given-names>AN</given-names></name>, <name name-style="western"><surname>Petric</surname><given-names>M</given-names></name>, et al.</person-group><article-title>Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus</article-title>. <source>J Gen Virol</source><year>2006</year>;<volume>87</volume>(<issue>3</issue>):<fpage>641</fpage>-<lpage>50</lpage><pub-id pub-id-type="pmid">16476986</pub-id></mixed-citation></ref><ref id="CIT0063"><label>63.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Graham</surname><given-names>RL</given-names></name>, <name name-style="western"><surname>Becker</surname><given-names>MM</given-names></name>, <name name-style="western"><surname>Eckerle</surname><given-names>LD</given-names></name>, et al.</person-group><article-title>A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease</article-title>. <source>Nat Med</source><year>2012</year>;<volume>18</volume>(<issue>12</issue>):<fpage>1820</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">23142821</pub-id></mixed-citation></ref><ref id="CIT0064"><label>64.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Qu</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Zheng</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Yao</surname><given-names>X</given-names></name>, et al.</person-group><article-title>Intranasal immunization with inactivated SARS-CoV (SARS-associated coronavirus) induced local and serum antibodies in mice</article-title>. <source>Vaccine</source><year>2005</year>;<volume>23</volume>(<issue>7</issue>):<fpage>924</fpage>-<lpage>31</lpage><pub-id pub-id-type="pmid">15603894</pub-id></mixed-citation></ref><ref id="CIT0065"><label>65.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Netland</surname><given-names>J</given-names></name>, <name name-style="western"><surname>DeDiego</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>J</given-names></name>, et al.</person-group><article-title>Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease</article-title>. <source>Virology</source><year>2010</year>;<volume>399</volume>(<issue>1</issue>):<fpage>120</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">20110095</pub-id></mixed-citation></ref><ref id="CIT0066"><label>66.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Fett</surname><given-names>C</given-names></name>, <name name-style="western"><surname>DeDiego</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Regla-Nava</surname><given-names>JA</given-names></name>, et al.</person-group><article-title>Complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking E protein</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>12</issue>):<fpage>6551</fpage>-<lpage>9</lpage><pub-id pub-id-type="pmid">23576515</pub-id></mixed-citation></ref><ref id="CIT0067"><label>67.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kim</surname><given-names>JH</given-names></name>, <name name-style="western"><surname>Jacob</surname><given-names>J. DN</given-names></name></person-group><article-title>A vaccines against influenza viruses</article-title>. <source>Curr Top Microbiol Immunol</source><year>2009</year>;<volume>333</volume>:<fpage>197</fpage>-<lpage>210</lpage><pub-id pub-id-type="pmid">19768407</pub-id></mixed-citation></ref><ref id="CIT0068"><label>68.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Khalil</surname><given-names>IA</given-names></name>, <name name-style="western"><surname>Kogure</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Akita</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Harashima</surname><given-names>H</given-names></name></person-group><article-title>Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery</article-title>. <source>Pharmacol Rev</source><year>2006</year>;<volume>58</volume>(<issue>1</issue>):<fpage>32</fpage>-<lpage>45</lpage><pub-id pub-id-type="pmid">16507881</pub-id></mixed-citation></ref><ref id="CIT0069"><label>69.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Šatkauskas</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Bureau</surname><given-names>MF</given-names></name>, <name name-style="western"><surname>Mahfoudi</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Mir</surname><given-names>LM</given-names></name></person-group><article-title>Slow accumulation of plasmid in muscle cells: supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis</article-title>. <source>Mol Ther</source><year>2001</year>;<volume>4</volume>(<issue>4</issue>):<fpage>317</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">11592834</pub-id></mixed-citation></ref><ref id="CIT0070"><label>70.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Shamlou</surname><given-names>PA</given-names></name></person-group><article-title>Scaleable processes for the manufacture of therapeutic quantities of plasmid DNA</article-title>. <source>Biotechnol Appl Biochem</source><year>2003</year>;<volume>37</volume>(<issue>3</issue>):<fpage>207</fpage>-<lpage>18</lpage><pub-id pub-id-type="pmid">12683955</pub-id></mixed-citation></ref><ref id="CIT0071"><label>71.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Prather</surname><given-names>KJ</given-names></name>, <name name-style="western"><surname>Sagar</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Murphy</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Chartrain</surname><given-names>M</given-names></name></person-group><article-title>Industrial scale production of plasmid DNA for vaccine and gene therapy: plasmid design, production, and purification</article-title>. <source>Enzyme Microb Technol</source><year>2003</year>;<volume>33</volume>(<issue>7</issue>):<fpage>865</fpage>-<lpage>83</lpage></mixed-citation></ref><ref id="CIT0072"><label>72.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hoare</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Levy</surname><given-names>MS</given-names></name>, <name name-style="western"><surname>Bracewell</surname><given-names>DG</given-names></name>, et al.</person-group><article-title>Bioprocess engineering issues that would be faced in producing a DNA vaccine at up to 100 m3 fermentation scale for an influenza pandemic</article-title>. <source>Biotechnol Prog</source><year>2005</year>;<volume>21</volume>(<issue>6</issue>):<fpage>1577</fpage>-<lpage>92</lpage><pub-id pub-id-type="pmid">16321039</pub-id></mixed-citation></ref><ref id="CIT0073"><label>73.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname><given-names>ZY</given-names></name>, <name name-style="western"><surname>Kong</surname><given-names>WP</given-names></name>, <name name-style="western"><surname>Huang</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice</article-title>. <source>Nature</source><year>2004</year>;<volume>428</volume>(<issue>6982</issue>):<fpage>561</fpage>-<lpage>4</lpage><pub-id pub-id-type="pmid">15024391</pub-id></mixed-citation></ref><ref id="CIT0074"><label>74.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhao</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Jin</surname><given-names>NY</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>RL</given-names></name>, et al.</person-group><article-title>Immunization of mice with a DNA vaccine based on severe acute respiratory syndrome coronavirus spike protein fragment 1</article-title>. <source>Viral Immunol</source><year>2006</year>;<volume>19</volume>(<issue>3</issue>):<fpage>518</fpage>-<lpage>24</lpage><pub-id pub-id-type="pmid">16987069</pub-id></mixed-citation></ref><ref id="CIT0075"><label>75.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Shi</surname><given-names>SQ</given-names></name>, <name name-style="western"><surname>Peng</surname><given-names>JP</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>YC</given-names></name>, et al.</person-group><article-title>The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization</article-title>. <source>Mol Immunol</source><year>2006</year>;<volume>43</volume>(<issue>11</issue>):<fpage>1791</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">16423399</pub-id></mixed-citation></ref><ref id="CIT0076"><label>76.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Roberts</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Lamirande</surname><given-names>EW</given-names></name>, <name name-style="western"><surname>Vogel</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Animal models and vaccines for SARS-CoV infection</article-title>. <source>Virus Res</source><year>2008</year>;<volume>133</volume>(<issue>1</issue>):<fpage>20</fpage>-<lpage>32</lpage><pub-id pub-id-type="pmid">17499378</pub-id></mixed-citation></ref><ref id="CIT0077"><label>77.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Tsoi</surname><given-names>HW</given-names></name>, et al.</person-group><article-title>SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike polypeptide from Escherichia coli as booster induces high titer of neutralizing antibody against SARS coronavirus</article-title>. <source>Vaccine</source><year>2005</year>;<volume>23</volume>(<issue>42</issue>):<fpage>4959</fpage>-<lpage>68</lpage><pub-id pub-id-type="pmid">15993989</pub-id></mixed-citation></ref><ref id="CIT0078"><label>78.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bisht</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Roberts</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Vogel</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice</article-title>. <source>Proc Natl Acad Sci USA</source><year>2004</year>;<volume>101</volume>(<issue>17</issue>):<fpage>6641</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">15096611</pub-id></mixed-citation></ref><ref id="CIT0079"><label>79.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bukreyev</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Lamirande</surname><given-names>EW</given-names></name>, <name name-style="western"><surname>Buchholz</surname><given-names>UJ</given-names></name>, et al.</person-group><article-title>Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS</article-title>. <source>Lancet</source><year>2004</year>;<volume>363</volume>(<issue>9427</issue>):<fpage>2122</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">15220033</pub-id></mixed-citation></ref><ref id="CIT0080"><label>80.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gao</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Tamin</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Soloff</surname><given-names>A</given-names></name>, et al.</person-group><article-title>Effects of a SARS-associated coronavirus vaccine in monkeys</article-title>. <source>Lancet</source><year>2003</year>;<volume>362</volume>(<issue>9399</issue>):<fpage>1895</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">14667748</pub-id></mixed-citation></ref><ref id="CIT0081"><label>81.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Lin</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection</article-title>. <source>J Immunol</source><year>2008</year>;<volume>180</volume>(<issue>2</issue>):<fpage>948</fpage>-<lpage>56</lpage><pub-id pub-id-type="pmid">18178835</pub-id></mixed-citation></ref><ref id="CIT0082"><label>82.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Lin</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection</article-title>. <source>Vaccine</source><year>2008</year>;<volume>26</volume>(<issue>13</issue>):<fpage>1644</fpage>-<lpage>51</lpage><pub-id pub-id-type="pmid">18289745</pub-id></mixed-citation></ref><ref id="CIT0083"><label>83.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Pichla-Gollon</surname><given-names>SL</given-names></name>, <name name-style="western"><surname>Lin</surname><given-names>S-W</given-names></name>, <name name-style="western"><surname>Hensley</surname><given-names>SE</given-names></name>, et al.</person-group><article-title>Effect of preexisting immunity on an adenovirus vaccine vector: in vitro neutralization assays fail to predict inhibition by antiviral antibody in vivo</article-title>. <source>J Virol</source><year>2009</year>;<volume>83</volume>(<issue>11</issue>):<fpage>5567</fpage>-<lpage>73</lpage><pub-id pub-id-type="pmid">19279092</pub-id></mixed-citation></ref><ref id="CIT0084"><label>84.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>Q</given-names></name>, <name name-style="western"><surname>Dai</surname><given-names>Z</given-names></name>, et al.</person-group><article-title>Adenovirus-based vaccines generate cytotoxic T lymphocytes to epitopes of NS1 from dengue virus that are present in all major serotypes</article-title>. <source>Hum Gene Ther</source><year>2008</year>;<volume>19</volume>(<issue>9</issue>):<fpage>927</fpage>-<lpage>36</lpage><pub-id pub-id-type="pmid">18788905</pub-id></mixed-citation></ref><ref id="CIT0085"><label>85.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Weingartl</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Czub</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Czub</surname><given-names>S</given-names></name>, et al.</person-group><article-title>Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets</article-title>. <source>J Virol</source><year>2004</year>;<volume>78</volume>(<issue>22</issue>):<fpage>12672</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">15507655</pub-id></mixed-citation></ref><ref id="CIT0086"><label>86.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lu</surname><given-names>X</given-names></name>, <name name-style="western"><surname>Chen</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Bai</surname><given-names>B</given-names></name>, et al.</person-group><article-title>Immune responses against severe acute respiratory syndrome coronavirus induced by virus‐like particles in mice</article-title>. <source>Immunology</source><year>2007</year>;<volume>122</volume>(<issue>4</issue>):<fpage>496</fpage>-<lpage>502</lpage><pub-id pub-id-type="pmid">17680799</pub-id></mixed-citation></ref><ref id="CIT0087"><label>87.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Liu</surname><given-names>YV</given-names></name>, <name name-style="western"><surname>Massare</surname><given-names>MJ</given-names></name>, <name name-style="western"><surname>Barnard</surname><given-names>DL</given-names></name>, et al.</person-group><article-title>Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV</article-title>. <source>Vaccine</source><year>2011</year>;<volume>29</volume>(<issue>38</issue>):<fpage>6606</fpage>-<lpage>13</lpage><pub-id pub-id-type="pmid">21762752</pub-id></mixed-citation></ref><ref id="CIT0088"><label>88.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lokugamage</surname><given-names>KG</given-names></name>, <name name-style="western"><surname>Yoshikawa-Iwata</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Ito</surname><given-names>N</given-names></name>, et al.</person-group><article-title>Chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (SCoV) S protein protect mice against challenge with SCoV</article-title>. <source>Vaccine</source><year>2008</year>;<volume>26</volume>(<issue>6</issue>):<fpage>797</fpage>-<lpage>808</lpage><pub-id pub-id-type="pmid">18191004</pub-id></mixed-citation></ref><ref id="CIT0089"><label>89.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ho</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Lin</surname><given-names>PH</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>CY</given-names></name>, et al.</person-group><article-title>Assembly of human severe acute respiratory syndrome coronavirus-like particles</article-title>. <source>Biochem Biophys Res Commun</source><year>2004</year>;<volume>318</volume>(<issue>4</issue>):<fpage>833</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">15147946</pub-id></mixed-citation></ref><ref id="CIT0090"><label>90.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Sailaja</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Skountzou</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Quan</surname><given-names>FS</given-names></name>, et al.</person-group><article-title>Human immunodeficiency virus-like particles activate multiple types of immune cells</article-title>. <source>Virology</source><year>2007</year>;<volume>362</volume>(<issue>2</issue>):<fpage>331</fpage>-<lpage>41</lpage><pub-id pub-id-type="pmid">17276476</pub-id></mixed-citation></ref><ref id="CIT0091"><label>91.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname><given-names>BZ</given-names></name>, <name name-style="western"><surname>Quan</surname><given-names>FS</given-names></name>, <name name-style="western"><surname>Kang</surname><given-names>SM</given-names></name>, et al.</person-group><article-title>Incorporation of membrane-anchored flagellin into influenza virus-like particles enhances the breadth of immune responses</article-title>. <source>J Virol</source><year>2008</year>;<volume>82</volume>(<issue>23</issue>):<fpage>11813</fpage>-<lpage>23</lpage><pub-id pub-id-type="pmid">18786995</pub-id></mixed-citation></ref><ref id="CIT0092"><label>92.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>He</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Zhou</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Wu</surname><given-names>H</given-names></name>, et al.</person-group><article-title>Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines</article-title>. <source>J Immunol</source><year>2004</year>;<volume>173</volume>(<issue>6</issue>):<fpage>4050</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">15356154</pub-id></mixed-citation></ref><ref id="CIT0093"><label>93.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ma</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal MERS vaccines</article-title>. <source>Vaccine</source><year>2014</year>;<volume>32</volume>(<issue>18</issue>):<fpage>2100</fpage>-<lpage>8</lpage><pub-id pub-id-type="pmid">24560617</pub-id></mixed-citation></ref><ref id="CIT0094"><label>94.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Agnihothram</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Gopal</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Yount</surname><given-names>BL</given-names></name>, et al.</person-group><article-title>Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses</article-title>. <source>J Infect Dis</source><year>2014</year>;<volume>209</volume>(<issue>7</issue>):<fpage>995</fpage>-<lpage>1006</lpage><pub-id pub-id-type="pmid">24253287</pub-id></mixed-citation></ref><ref id="CIT0095"><label>95.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Naz</surname><given-names>RK</given-names></name>, <name name-style="western"><surname>Dabir</surname><given-names>P</given-names></name></person-group><article-title>Peptide vaccines against cancer, infectious diseases, and conception</article-title>. <source>Front Biosci</source><year>2006</year>;<volume>12</volume>:<fpage>1833</fpage>-<lpage>44</lpage></mixed-citation></ref><ref id="CIT0096"><label>96.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Reed</surname><given-names>SG</given-names></name>, <name name-style="western"><surname>Bertholet</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Coler</surname><given-names>RN</given-names></name>, <name name-style="western"><surname>Friede</surname><given-names>M</given-names></name></person-group><article-title>New horizons in adjuvants for vaccine development</article-title>. <source>Trends Immunol</source><year>2009</year>;<volume>30</volume>(<issue>1</issue>):<fpage>23</fpage>-<lpage>32</lpage><pub-id pub-id-type="pmid">19059004</pub-id></mixed-citation></ref><ref id="CIT0097"><label>97.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Marciani</surname><given-names>DJ</given-names></name></person-group><article-title>Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity</article-title>. <source>Drug Discov Today</source><year>2003</year>;<volume>8</volume>(<issue>20</issue>):<fpage>934</fpage>-<lpage>43</lpage><pub-id pub-id-type="pmid">14554157</pub-id></mixed-citation></ref><ref id="CIT0098"><label>98.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lambert</surname><given-names>SL</given-names></name>, <name name-style="western"><surname>Yang</surname><given-names>CF</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>Z</given-names></name>, et al.</person-group><article-title>Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant glucopyranosyl Lipid A</article-title>. <source>PLoS One</source><year>2012</year>;<volume>7</volume>(<issue>12</issue>):<fpage>e51618</fpage><pub-id pub-id-type="pmid">23284726</pub-id></mixed-citation></ref><ref id="CIT0099"><label>99.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Podda</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Del Giudice</surname><given-names>G. MF</given-names></name></person-group><article-title>59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile</article-title>. <source>Expert Rev Vaccines</source><year>2003</year>;<volume>2</volume>(<issue>2</issue>):<fpage>197</fpage>-<lpage>204</lpage><pub-id pub-id-type="pmid">12899571</pub-id></mixed-citation></ref><ref id="CIT0100"><label>100.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Radošević</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Rodriguez</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Mintardjo</surname><given-names>R</given-names></name>, et al.</person-group><article-title>Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: impact of distinct additional adjuvants</article-title>. <source>Vaccine</source><year>2008</year>;<volume>26</volume>(<issue>29</issue>):<fpage>3640</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">18514980</pub-id></mixed-citation></ref><ref id="CIT0101"><label>101.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Baldwin</surname><given-names>SL</given-names></name>, <name name-style="western"><surname>Bertholet</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Reese</surname><given-names>VA</given-names></name>, et al.</person-group><article-title>The importance of adjuvant formulation in the development of a tuberculosis vaccine</article-title>. <source>J Immunol</source><year>2012</year>;<volume>188</volume>(<issue>5</issue>):<fpage>2189</fpage>-<lpage>97</lpage><pub-id pub-id-type="pmid">22291184</pub-id></mixed-citation></ref><ref id="CIT0102"><label>102.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Filipazzi</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Pilla</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Mariani</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Limited induction of tumor cross-reactive T cells without a measurable clinical benefit in early melanoma patients vaccinated with human leukocyte antigen class I–modified peptides</article-title>. <source>Clin Cancer Res</source><year>2012</year>;<volume>18</volume>(<issue>23</issue>):<fpage>6485</fpage>-<lpage>96</lpage><pub-id pub-id-type="pmid">23032742</pub-id></mixed-citation></ref><ref id="CIT0103"><label>103.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mavroudis</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Bolonakis</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Cornet</surname><given-names>S</given-names></name>, et al.</person-group><article-title>A phase I study of the optimized cryptic peptide TERT572Y in patients with advanced malignancies</article-title>. <source>Oncology</source><year>2006</year>;<volume>70</volume>(<issue>4</issue>):<fpage>306</fpage>-<lpage>14</lpage><pub-id pub-id-type="pmid">17047402</pub-id></mixed-citation></ref><ref id="CIT0104"><label>104.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Sun</surname><given-names>S</given-names></name>, et al.</person-group><article-title>A critical HA1 neutralizing domain of H5N1 influenza in an optimal conformation induces strong cross-protection</article-title>. <source>PLoS One</source><year>2013</year>;<volume>8</volume>(<issue>1</issue>):<fpage>e53568</fpage><pub-id pub-id-type="pmid">23320093</pub-id></mixed-citation></ref><ref id="CIT0105"><label>105.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Budimir</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Haan</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Meijerhof</surname><given-names>T</given-names></name>, et al.</person-group><article-title>Heterosubtypic cross‐protection induced by whole inactivated influenza virus vaccine in mice: influence of the route of vaccine administration</article-title>. <source>Influenza Other Respir Viruses</source><year>2013</year>;<volume>7</volume>(<issue>6</issue>):<fpage>1202</fpage>-<lpage>9</lpage><pub-id pub-id-type="pmid">24102979</pub-id></mixed-citation></ref><ref id="CIT0106"><label>106.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Frenck</surname><given-names>RW</given-names><suffix>Jr</suffix></name>, <name name-style="western"><surname>Belshe</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Brady</surname><given-names>RC</given-names></name>, et al.</person-group><article-title>Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone<sup>®</sup>) administered by intradermal and intramuscular route in healthy adults</article-title>. <source>Vaccine</source><year>2011</year>;<volume>29</volume>(<issue>34</issue>):<fpage>5666</fpage>-<lpage>74</lpage><pub-id pub-id-type="pmid">21699951</pub-id></mixed-citation></ref><ref id="CIT0107"><label>107.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Rahman</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Dahmen</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Herzog‐Hauff</surname><given-names>S</given-names></name>, et al.</person-group><article-title>Cellular and humoral immune responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen</article-title>. <source>Hepatology</source><year>2000</year>;<volume>31</volume>(<issue>2</issue>):<fpage>521</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">10655280</pub-id></mixed-citation></ref><ref id="CIT0108"><label>108.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mooney</surname><given-names>AJ</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Gabbard</surname><given-names>JD</given-names></name>, et al.</person-group><article-title>Recombinant parainfluenza virus 5 vaccine encoding the influenza virus hemagglutinin protects against H5N1 highly pathogenic avian influenza virus infection following intranasal or intramuscular vaccination of BALB/c mice</article-title>. <source>J Virol</source><year>2013</year>;<volume>87</volume>(<issue>1</issue>):<fpage>363</fpage>-<lpage>71</lpage><pub-id pub-id-type="pmid">23077318</pub-id></mixed-citation></ref><ref id="CIT0109"><label>109.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Siu</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Teoh</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Lo</surname><given-names>J</given-names></name>, et al.</person-group><article-title>The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles</article-title>. <source>J Virol</source><year>2008</year>;<volume>82</volume>(<issue>22</issue>):<fpage>11318</fpage>-<lpage>30</lpage><pub-id pub-id-type="pmid">18753196</pub-id></mixed-citation></ref><ref id="CIT0110"><label>110.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kitabatake</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Inoue</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Yasui</surname><given-names>F</given-names></name>, et al.</person-group><article-title>SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus</article-title>. <source>Vaccine</source><year>2007</year>;<volume>25</volume>(<issue>4</issue>):<fpage>630</fpage>-<lpage>7</lpage><pub-id pub-id-type="pmid">17011679</pub-id></mixed-citation></ref><ref id="CIT0111"><label>111.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Takasuka</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Fujii</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Takahashi</surname><given-names>Y</given-names></name>, et al.</person-group><article-title>A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</article-title>. <source>Int Immunol</source><year>2004</year>;<volume>16</volume>(<issue>10</issue>):<fpage>1423</fpage>-<lpage>30</lpage><pub-id pub-id-type="pmid">15314040</pub-id></mixed-citation></ref><ref id="CIT0112"><label>112.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Zhao</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>L</given-names></name>, et al.</person-group><article-title>Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells</article-title>. <source>Biochem Biophys Res Commun</source><year>2009</year>;<volume>384</volume>(<issue>4</issue>):<fpage>486</fpage>-<lpage>90</lpage><pub-id pub-id-type="pmid">19422787</pub-id></mixed-citation></ref><ref id="CIT0113"><label>113.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Khosrow Tayebati</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Ejike Nwankwo</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Amenta</surname><given-names>F</given-names></name></person-group><article-title>Intranasal drug delivery to the central nervous system: present status and future outlook</article-title>. <source>Curr Pharm Des</source><year>2013</year>;<volume>19</volume>(<issue>3</issue>):<fpage>510</fpage>-<lpage>26</lpage><pub-id pub-id-type="pmid">23116337</pub-id></mixed-citation></ref><ref id="CIT0114"><label>114.</label><mixed-citation publication-type="web"><person-group person-group-type="author"><collab>CDC</collab></person-group><article-title>Seasonal Influenza (Flu)</article-title>. <comment>Available from:</comment><ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/flu/protect/whoshouldvax.htm">www.cdc.gov/flu/protect/whoshouldvax.htm</ext-link><comment>[Last accessed on 24 March 2014]</comment></mixed-citation></ref><ref id="CIT0115"><label>115.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Liew</surname><given-names>FY</given-names></name>, <name name-style="western"><surname>Russell</surname><given-names>SM</given-names></name>, <name name-style="western"><surname>Appleyard</surname><given-names>G</given-names></name>, et al.</person-group><article-title>Cross‐protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity</article-title>. <source>Eur J Immunol</source><year>1984</year>;<volume>14</volume>(<issue>4</issue>):<fpage>350</fpage>-<lpage>6</lpage><pub-id pub-id-type="pmid">6609824</pub-id></mixed-citation></ref><ref id="CIT0116"><label>116.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kuiken</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Fouchier</surname><given-names>RA</given-names></name>, <name name-style="western"><surname>Schutten</surname><given-names>M</given-names></name>, et al.</person-group><article-title>Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome</article-title>. <source>Lancet</source><year>2003</year>;<volume>362</volume>(<issue>9380</issue>):<fpage>263</fpage>-<lpage>70</lpage><pub-id pub-id-type="pmid">12892955</pub-id></mixed-citation></ref><ref id="CIT0117"><label>117.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Martina</surname><given-names>BE</given-names></name>, <name name-style="western"><surname>Haagmans</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Kuiken</surname><given-names>T</given-names></name>, et al.</person-group><article-title>Virology: SARS virus infection of cats and ferrets</article-title>. <source>Nature</source><year>2003</year>;<volume>425</volume>(<issue>6961</issue>):<fpage>915</fpage>-<lpage>15</lpage><pub-id pub-id-type="pmid">14586458</pub-id></mixed-citation></ref><ref id="CIT0118"><label>118.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Roberts</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Vogel</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Guarner</surname><given-names>J</given-names></name>, et al.</person-group><article-title>Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters</article-title>. <source>J Virol</source><year>2005</year>;<volume>79</volume>(<issue>1</issue>):<fpage>503</fpage>-<lpage>11</lpage><pub-id pub-id-type="pmid">15596843</pub-id></mixed-citation></ref><ref id="CIT0119"><label>119.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>de Wit</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Prescott</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Baseler</surname><given-names>L</given-names></name>, et al.</person-group><article-title>The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters</article-title>. <source>PLoS One</source><year>2013</year>;<volume>8</volume>(<issue>7</issue>):<fpage>e69127</fpage><pub-id pub-id-type="pmid">23844250</pub-id></mixed-citation></ref><ref id="CIT0120"><label>120.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yao</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Bao</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Deng</surname><given-names>W</given-names></name>, et al.</person-group><article-title>An animal model of MERS produced by infection of Rhesus macaques with MERS coronavirus</article-title>. <source>J Infect Dis</source><year>2014</year>;<volume>209</volume>(<issue>2</issue>):<fpage>236</fpage>-<lpage>42</lpage><pub-id pub-id-type="pmid">24218506</pub-id></mixed-citation></ref><ref id="CIT0121"><label>121.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Coleman</surname><given-names>CM</given-names></name>, <name name-style="western"><surname>Matthews</surname><given-names>KL</given-names></name>, <name name-style="western"><surname>Goicochea</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Frieman</surname><given-names>MB</given-names></name></person-group><article-title>Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus</article-title>. <source>J Gen Virol</source><year>2014</year>;<volume>95</volume>(<issue>Pt 2</issue>):<fpage>408</fpage>-<lpage>12</lpage><pub-id pub-id-type="pmid">24197535</pub-id></mixed-citation></ref><ref id="CIT0122"><label>122.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Falzarano</surname><given-names>D</given-names></name>, <name name-style="western"><surname>de Wit</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Rasmussen</surname><given-names>AL</given-names></name>, et al.</person-group><article-title>Treatment with interferon-[alpha] 2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques</article-title>. <source>Nat Med</source><year>2013</year>;<volume>19</volume>(<issue>10</issue>):<fpage>1313</fpage>-<lpage>17</lpage><pub-id pub-id-type="pmid">24013700</pub-id></mixed-citation></ref><ref id="CIT0123"><label>123.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Munster</surname><given-names>VJ</given-names></name>, <name name-style="western"><surname>de Wit</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Feldmann</surname><given-names>H</given-names></name></person-group><article-title>Pneumonia from human coronavirus in a macaque model</article-title>. <source>N Engl J Med</source><year>2013</year>;<volume>368</volume>(<issue>16</issue>):<fpage>1560</fpage>-<lpage>2</lpage></mixed-citation></ref><ref id="CIT0124"><label>124.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>de Wit</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Rasmussen</surname><given-names>AL</given-names></name>, <name name-style="western"><surname>Falzarano</surname><given-names>D</given-names></name>, et al.</person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques</article-title>. <source>Proc Natl Acad Sci USA</source><year>2013</year>;<volume>110</volume>(<issue>41</issue>):<fpage>16598</fpage>-<lpage>603</lpage><pub-id pub-id-type="pmid">24062443</pub-id></mixed-citation></ref><ref id="CIT0125"><label>125.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Devitt</surname><given-names>E</given-names></name></person-group><article-title>Lack of small animal model hinders MERS coronavirus research</article-title>. <source>Nat Med</source><year>2013</year>;<volume>19</volume>(<issue>8</issue>):<fpage>952</fpage>-<lpage>2</lpage><pub-id pub-id-type="pmid">23921729</pub-id></mixed-citation></ref><ref id="CIT0126"><label>126.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhao</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Wohlford-Lenane</surname><given-names>C</given-names></name>, et al.</person-group><article-title>Rapid generation of a mouse model for Middle East respiratory syndrome</article-title>. <source>Proc Natl Acad Sci USA</source><year>2014</year>;<volume>111</volume>(<issue>13</issue>):<fpage>4970</fpage>-<lpage>5</lpage><pub-id pub-id-type="pmid">24599590</pub-id></mixed-citation></ref><ref id="CIT0127"><label>127.</label><mixed-citation publication-type="web"><person-group person-group-type="author"><name name-style="western"><surname>Reardon</surname><given-names>S</given-names></name></person-group><article-title>Nature news</article-title>. <comment>Available from:</comment><ext-link ext-link-type="uri" xlink:href="http://www.nature.com/news/biologists-make-first-mouse-model-for-mers-1.14634">www.nature.com/news/biologists-make-first-mouse-model-for-mers-1.14634</ext-link><comment>[Last accessed on 22 March 2014]</comment></mixed-citation></ref><ref id="CIT0128"><label>128.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Narayanan</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Maeda</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Maeda</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Makino</surname><given-names>S</given-names></name></person-group><article-title>Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells</article-title>. <source>J Virol</source><year>2000</year>;<volume>74</volume>(<issue>17</issue>):<fpage>8127</fpage>-<lpage>34</lpage><pub-id 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