A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model
Identifieur interne : 000434 ( Pmc/Checkpoint ); précédent : 000433; suivant : 000435A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model
Auteurs : Anwar M. Hashem [Arabie saoudite] ; Abdullah Algaissi ; Anurodh Shankar Agrawal ; Sawsan S. Al-Amri [Arabie saoudite] ; Rowa Y. Alhabbab [Arabie saoudite] ; Sayed S. Sohrab [Arabie saoudite] ; Abdulrahman S. Almasoud [Arabie saoudite] ; Naif Khalaf Alharbi [Arabie saoudite] ; Bi-Hung Peng ; Marsha Russell [Canada] ; Xuguang Li [Canada] ; Chien-Te K. TsengSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2019.
Abstract
Infection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted.
We extended and optimized our previous recombinant adenovirus 5 (rAd5)–based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg+) mice.
Immunization of hDPP4 Tg+ mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1– but not rAd5-S1/F/CD40L–immunized mice exhibited marked pulmonary perivascular hemorrhage post–MERS-CoV challenge despite the observed protection.
Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.
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DOI: 10.1093/infdis/jiz137
PubMed: 30911758
PubMed Central: 7107499
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model</title><author><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M" last="Hashem">Anwar M. Hashem</name><affiliation><nlm:aff id="AF0001"><institution>Department of Medical Microbiology and Parasitology, Faculty of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0005"><institution>Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University</institution></nlm:aff></affiliation></author><author><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Al Amri, Sawsan S" sort="Al Amri, Sawsan S" uniqKey="Al Amri S" first="Sawsan S" last="Al-Amri">Sawsan S. Al-Amri</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y" last="Alhabbab">Rowa Y. Alhabbab</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0006"><institution>Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sohrab, Sayed S" sort="Sohrab, Sayed S" uniqKey="Sohrab S" first="Sayed S" last="Sohrab">Sayed S. Sohrab</name><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="S Almasoud, Abdulrahman" sort="S Almasoud, Abdulrahman" uniqKey="S Almasoud A" first="Abdulrahman" last="S. Almasoud">Abdulrahman S. Almasoud</name><affiliation wicri:level="1"><nlm:aff id="AF0007"><institution>Department of Infectious Disease Research, King Abdullah International Medical Research Center</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alharbi, Naif Khalaf" sort="Alharbi, Naif Khalaf" uniqKey="Alharbi N" first="Naif Khalaf" last="Alharbi">Naif Khalaf Alharbi</name><affiliation wicri:level="1"><nlm:aff id="AF0007"><institution>Department of Infectious Disease Research, King Abdullah International Medical Research Center</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><affiliation><nlm:aff id="AF0008"><institution>Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Russell, Marsha" sort="Russell, Marsha" uniqKey="Russell M" first="Marsha" last="Russell">Marsha Russell</name><affiliation wicri:level="2"><nlm:aff id="AF0009"><institution>Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada</institution>, Ottawa, Ontario</nlm:aff><country>Canada</country><placeName><region type="province">Ontario</region></placeName><wicri:cityArea>, Ottawa</wicri:cityArea></affiliation></author><author><name sortKey="Li, Xuguang" sort="Li, Xuguang" uniqKey="Li X" first="Xuguang" last="Li">Xuguang Li</name><affiliation wicri:level="2"><nlm:aff id="AF0009"><institution>Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada</institution>, Ottawa, Ontario</nlm:aff><country>Canada</country><placeName><region type="province">Ontario</region></placeName><wicri:cityArea>, Ottawa</wicri:cityArea></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0010"><institution>Center of Biodefense and Emerging Disease, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30911758</idno><idno type="pmc">7107499</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107499</idno><idno type="RBID">PMC:7107499</idno><idno type="doi">10.1093/infdis/jiz137</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000E34</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E34</idno><idno type="wicri:Area/Pmc/Curation">000E34</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E34</idno><idno type="wicri:Area/Pmc/Checkpoint">000434</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000434</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model</title><author><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M" last="Hashem">Anwar M. Hashem</name><affiliation><nlm:aff id="AF0001"><institution>Department of Medical Microbiology and Parasitology, Faculty of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0005"><institution>Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University</institution></nlm:aff></affiliation></author><author><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Al Amri, Sawsan S" sort="Al Amri, Sawsan S" uniqKey="Al Amri S" first="Sawsan S" last="Al-Amri">Sawsan S. Al-Amri</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y" last="Alhabbab">Rowa Y. Alhabbab</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0006"><institution>Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sohrab, Sayed S" sort="Sohrab, Sayed S" uniqKey="Sohrab S" first="Sayed S" last="Sohrab">Sayed S. Sohrab</name><affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="S Almasoud, Abdulrahman" sort="S Almasoud, Abdulrahman" uniqKey="S Almasoud A" first="Abdulrahman" last="S. Almasoud">Abdulrahman S. Almasoud</name><affiliation wicri:level="1"><nlm:aff id="AF0007"><institution>Department of Infectious Disease Research, King Abdullah International Medical Research Center</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alharbi, Naif Khalaf" sort="Alharbi, Naif Khalaf" uniqKey="Alharbi N" first="Naif Khalaf" last="Alharbi">Naif Khalaf Alharbi</name><affiliation wicri:level="1"><nlm:aff id="AF0007"><institution>Department of Infectious Disease Research, King Abdullah International Medical Research Center</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><affiliation><nlm:aff id="AF0008"><institution>Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Russell, Marsha" sort="Russell, Marsha" uniqKey="Russell M" first="Marsha" last="Russell">Marsha Russell</name><affiliation wicri:level="2"><nlm:aff id="AF0009"><institution>Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada</institution>, Ottawa, Ontario</nlm:aff><country>Canada</country><placeName><region type="province">Ontario</region></placeName><wicri:cityArea>, Ottawa</wicri:cityArea></affiliation></author><author><name sortKey="Li, Xuguang" sort="Li, Xuguang" uniqKey="Li X" first="Xuguang" last="Li">Xuguang Li</name><affiliation wicri:level="2"><nlm:aff id="AF0009"><institution>Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada</institution>, Ottawa, Ontario</nlm:aff><country>Canada</country><placeName><region type="province">Ontario</region></placeName><wicri:cityArea>, Ottawa</wicri:cityArea></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><affiliation><nlm:aff id="AF0004"><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0010"><institution>Center of Biodefense and Emerging Disease, University of Texas Medical Branch</institution>, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><sec id="s0100"><title>Background</title><p>Infection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted.</p></sec><sec id="s0101"><title>Methods</title><p>We extended and optimized our previous recombinant adenovirus 5 (rAd5)–based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg<sup>+</sup>) mice.</p></sec><sec id="s0102"><title>Results</title><p>Immunization of hDPP4 Tg<sup>+</sup> mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1– but not rAd5-S1/F/CD40L–immunized mice exhibited marked pulmonary perivascular hemorrhage post–MERS-CoV challenge despite the observed protection.</p></sec><sec id="s0103"><title>Conclusions</title><p>Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.</p></sec></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><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Park, Sh" uniqKey="Park S">SH Park</name></author><author><name sortKey="Kim, Ys" uniqKey="Kim Y">YS Kim</name></author><author><name sortKey="Jung, Y" uniqKey="Jung Y">Y Jung</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="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="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</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="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name></author><author><name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W Shi</name></author><author><name sortKey="Joyce, Mg" uniqKey="Joyce M">MG Joyce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name></author><author><name sortKey="Liu, Yv" uniqKey="Liu Y">YV Liu</name></author><author><name sortKey="Mu, H" uniqKey="Mu H">H Mu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Amri, Ss" uniqKey="Al Amri S">SS Al-Amri</name></author><author><name sortKey="Abbas, At" uniqKey="Abbas A">AT Abbas</name></author><author><name sortKey="Siddiq, La" uniqKey="Siddiq L">LA Siddiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</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="Guo, X" uniqKey="Guo X">X Guo</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y Deng</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Van Den Brand, Jm" uniqKey="Van Den Brand J">JM van den Brand</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muthumani, K" uniqKey="Muthumani K">K Muthumani</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="Reuschel, El" uniqKey="Reuschel E">EL Reuschel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alharbi, Nk" uniqKey="Alharbi N">NK Alharbi</name></author><author><name sortKey="Padron Regalado, E" uniqKey="Padron Regalado E">E Padron-Regalado</name></author><author><name sortKey="Thompson, Cp" uniqKey="Thompson C">CP Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</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="Tseng, Ct" uniqKey="Tseng C">CT Tseng</name></author><author><name sortKey="Sbrana, E" uniqKey="Sbrana E">E Sbrana</name></author><author><name sortKey="Iwata Yoshikawa, N" uniqKey="Iwata Yoshikawa N">N Iwata-Yoshikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Zy" uniqKey="Yang Z">ZY Yang</name></author><author><name sortKey="Werner, Hc" uniqKey="Werner H">HC Werner</name></author><author><name sortKey="Kong, Wp" uniqKey="Kong W">WP Kong</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><author><name sortKey="He, R" uniqKey="He R">R He</name></author><author><name sortKey="Cao, J" uniqKey="Cao J">J Cao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deming, D" uniqKey="Deming D">D Deming</name></author><author><name sortKey="Sheahan, T" uniqKey="Sheahan T">T Sheahan</name></author><author><name sortKey="Heise, M" uniqKey="Heise M">M Heise</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaume, M" uniqKey="Jaume M">M Jaume</name></author><author><name sortKey="Yip, Ms" uniqKey="Yip M">MS Yip</name></author><author><name sortKey="Kam, Yw" uniqKey="Kam Y">YW Kam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author><author><name sortKey="Corapi, Wv" uniqKey="Corapi W">WV Corapi</name></author><author><name sortKey="Ngichabe, Ck" uniqKey="Ngichabe C">CK Ngichabe</name></author><author><name sortKey="Baines, Jd" uniqKey="Baines J">JD Baines</name></author><author><name sortKey="Scott, Fw" uniqKey="Scott F">FW Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, Rc" uniqKey="Weiss R">RC Weiss</name></author><author><name sortKey="Scott, Fw" uniqKey="Scott F">FW Scott</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="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</name></author><author><name sortKey="Algaissi, A" uniqKey="Algaissi A">A Algaissi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Kooten, C" uniqKey="Van Kooten C">C van Kooten</name></author><author><name sortKey="Banchereau, J" uniqKey="Banchereau J">J Banchereau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, Dy" uniqKey="Ma D">DY Ma</name></author><author><name sortKey="Clark, Ea" uniqKey="Clark E">EA Clark</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bishop, Ga" uniqKey="Bishop G">GA Bishop</name></author><author><name sortKey="Hostager, Bs" uniqKey="Hostager B">BS Hostager</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allen, Rc" uniqKey="Allen R">RC Allen</name></author><author><name sortKey="Armitage, Rj" uniqKey="Armitage R">RJ Armitage</name></author><author><name sortKey="Conley, Me" uniqKey="Conley M">ME Conley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cao, J" uniqKey="Cao J">J Cao</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Du, Y" uniqKey="Du Y">Y Du</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Jiang, P" uniqKey="Jiang P">P Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="G Mez, Ce" uniqKey="G Mez C">CE Gómez</name></author><author><name sortKey="Najera, Jl" uniqKey="Najera J">JL Nájera</name></author><author><name sortKey="Sanchez, R" uniqKey="Sanchez R">R Sánchez</name></author><author><name sortKey="Jimenez, V" uniqKey="Jimenez V">V Jiménez</name></author><author><name sortKey="Esteban, M" uniqKey="Esteban M">M Esteban</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, D" uniqKey="Huang D">D Huang</name></author><author><name sortKey="Pereboev, Av" uniqKey="Pereboev A">AV Pereboev</name></author><author><name sortKey="Korokhov, N" uniqKey="Korokhov N">N Korokhov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, Q" uniqKey="Yao Q">Q Yao</name></author><author><name sortKey="Fischer, Kp" uniqKey="Fischer K">KP Fischer</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hashem, Am" uniqKey="Hashem A">AM Hashem</name></author><author><name sortKey="Gravel, C" uniqKey="Gravel C">C Gravel</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, X" uniqKey="Fan X">X Fan</name></author><author><name sortKey="Hashem, Am" uniqKey="Hashem A">AM Hashem</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grehan, K" uniqKey="Grehan K">K Grehan</name></author><author><name sortKey="Ferrara, F" uniqKey="Ferrara F">F Ferrara</name></author><author><name sortKey="Temperton, N" uniqKey="Temperton N">N Temperton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T Garron</name></author><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, E" uniqKey="Kim E">E Kim</name></author><author><name sortKey="Okada, K" uniqKey="Okada K">K Okada</name></author><author><name sortKey="Kenniston, T" uniqKey="Kenniston T">T Kenniston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="Wells, D" uniqKey="Wells D">D Wells</name></author><author><name sortKey="Lambe, T" uniqKey="Lambe T">T Lambe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Tr" uniqKey="Johnson T">TR Johnson</name></author><author><name sortKey="Parker, Ra" uniqKey="Parker R">RA Parker</name></author><author><name sortKey="Johnson, Je" uniqKey="Johnson J">JE Johnson</name></author><author><name sortKey="Graham, Bs" uniqKey="Graham B">BS Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kapikian, Az" uniqKey="Kapikian A">AZ Kapikian</name></author><author><name sortKey="Mitchell, Rh" uniqKey="Mitchell R">RH Mitchell</name></author><author><name sortKey="Chanock, Rm" uniqKey="Chanock R">RM Chanock</name></author><author><name sortKey="Shvedoff, Ra" uniqKey="Shvedoff R">RA Shvedoff</name></author><author><name sortKey="Stewart, Ce" uniqKey="Stewart C">CE Stewart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Hw" uniqKey="Kim H">HW Kim</name></author><author><name sortKey="Canchola, Jg" uniqKey="Canchola J">JG Canchola</name></author><author><name sortKey="Brandt, Cd" uniqKey="Brandt C">CD Brandt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tai, W" uniqKey="Tai W">W Tai</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="Volz, A" uniqKey="Volz A">A Volz</name></author><author><name sortKey="Kupke, A" uniqKey="Kupke A">A Kupke</name></author><author><name sortKey="Song, F" uniqKey="Song F">F Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malczyk, Ah" uniqKey="Malczyk A">AH Malczyk</name></author><author><name sortKey="Kupke, A" uniqKey="Kupke A">A Kupke</name></author><author><name sortKey="Prufer, S" uniqKey="Prufer S">S Prüfer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N van Doremalen</name></author><author><name sortKey="Hijazeen, Zs" uniqKey="Hijazeen Z">ZS Hijazeen</name></author><author><name sortKey="Holloway, P" uniqKey="Holloway P">P Holloway</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></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>Oxford University Press</publisher-name><publisher-loc>US</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30911758</article-id><article-id pub-id-type="pmc">7107499</article-id><article-id pub-id-type="doi">10.1093/infdis/jiz137</article-id><article-id pub-id-type="publisher-id">jiz137</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject><subj-group subj-group-type="category-toc-heading"><subject>Vaccines</subject></subj-group></subj-group></article-categories><title-group><article-title>A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-8471-7011</contrib-id><name><surname>Hashem</surname><given-names>Anwar M</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="author-notes" rid="fn0001"></xref><xref ref-type="corresp" rid="c1"></xref><pmc-comment>amhashem@kau.edu.sa </pmc-comment>
</contrib><contrib contrib-type="author"><name><surname>Algaissi</surname><given-names>Abdullah</given-names></name><xref ref-type="aff" rid="AF0004">4</xref><xref ref-type="aff" rid="AF0005">5</xref><xref ref-type="author-notes" rid="fn0001"></xref></contrib><contrib contrib-type="author"><name><surname>Agrawal</surname><given-names>Anurodh Shankar</given-names></name><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Al-amri</surname><given-names>Sawsan S</given-names></name><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref></contrib><contrib contrib-type="author"><name><surname>Alhabbab</surname><given-names>Rowa Y</given-names></name><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0006">6</xref></contrib><contrib contrib-type="author"><name><surname>Sohrab</surname><given-names>Sayed S</given-names></name><xref ref-type="aff" rid="AF0003">3</xref></contrib><contrib contrib-type="author"><name><surname>S. Almasoud</surname><given-names>Abdulrahman</given-names></name><xref ref-type="aff" rid="AF0007">7</xref></contrib><contrib contrib-type="author"><name><surname>Alharbi</surname><given-names>Naif Khalaf</given-names></name><xref ref-type="aff" rid="AF0007">7</xref></contrib><contrib contrib-type="author"><name><surname>Peng</surname><given-names>Bi-Hung</given-names></name><xref ref-type="aff" rid="AF0008">8</xref></contrib><contrib contrib-type="author"><name><surname>Russell</surname><given-names>Marsha</given-names></name><xref ref-type="aff" rid="AF0009">9</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Xuguang</given-names></name><xref ref-type="aff" rid="AF0009">9</xref></contrib><contrib contrib-type="author"><name><surname>Tseng</surname><given-names>Chien-Te K</given-names></name><xref ref-type="aff" rid="AF0004">4</xref><xref ref-type="aff" rid="AF0010">10</xref></contrib></contrib-group><aff id="AF0001"><label>1</label><institution>Department of Medical Microbiology and Parasitology, Faculty of Medicine</institution></aff><aff id="AF0002"><label>2</label><institution>Vaccines and Immunotherapy Unit, King Fahd Medical Research Center</institution>,<country country="SA">Saudi Arabia</country></aff><aff id="AF0003"><label>3</label><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University</institution>, Jeddah,<country country="SA">Saudi Arabia</country></aff><aff id="AF0004"><label>4</label><institution>Department of Microbiology and Immunology, University of Texas Medical Branch</institution>, Galveston</aff><aff id="AF0005"><label>5</label><institution>Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University</institution></aff><aff id="AF0006"><label>6</label><institution>Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University</institution>, Jeddah</aff><aff id="AF0007"><label>7</label><institution>Department of Infectious Disease Research, King Abdullah International Medical Research Center</institution>, Riyadh,<country country="SA">Saudi Arabia</country></aff><aff id="AF0008"><label>8</label><institution>Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch</institution>, Galveston</aff><aff id="AF0009"><label>9</label><institution>Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada</institution>, Ottawa, Ontario</aff><aff id="AF0010"><label>10</label><institution>Center of Biodefense and Emerging Disease, University of Texas Medical Branch</institution>, Galveston</aff><author-notes><fn id="fn0001"><p>A. M. H. and A. A. contributed equally to this study and co-first authors.</p></fn><corresp id="c1">Correspondence: Anwar M. Hashem, PhD, Department of Medical Microbiology and Parasitology, Faculty of Medicine and Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80205, Jeddah 21859, Saudi Arabia. (<email>amhashem@kau.edu.sa</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="epub" iso-8601-date="2019-07-04"><day>04</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>08</day><month>10</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 12 months and
0 days and was based on the
<volume>220</volume><issue>10</issue><fpage>1558</fpage><lpage>1567</lpage><history><date date-type="received"><day>08</day><month>1</month><year>2019</year></date><date date-type="accepted"><day>21</day><month>3</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</copyright-statement><copyright-year>2019</copyright-year><license license-type="publisher-standard" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"><license-p>This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (<ext-link ext-link-type="uri" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model">https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model</ext-link>)</license-p></license><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 xlink:href="jiz137.pdf"></self-uri><abstract><title>Abstract</title><sec id="s0100"><title>Background</title><p>Infection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted.</p></sec><sec id="s0101"><title>Methods</title><p>We extended and optimized our previous recombinant adenovirus 5 (rAd5)–based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg<sup>+</sup>) mice.</p></sec><sec id="s0102"><title>Results</title><p>Immunization of hDPP4 Tg<sup>+</sup> mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1– but not rAd5-S1/F/CD40L–immunized mice exhibited marked pulmonary perivascular hemorrhage post–MERS-CoV challenge despite the observed protection.</p></sec><sec id="s0103"><title>Conclusions</title><p>Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.</p></sec></abstract><abstract abstract-type="teaser"><p>In this study, we describe a potent and safe recombinant adenovirus 5–based Middle East respiratory syndrome coronavirus (MERS-CoV) vaccine expressing MERS-CoV S1 as an antigen and incorporating CD40L as a targeting ligand and molecular adjuvant. The vaccine protected transgenic mice against lethal challenge without vaccine-associated immunopathology.</p></abstract><kwd-group><kwd>MERS-CoV</kwd><kwd>vaccine</kwd><kwd>immunopathology</kwd><kwd>CD40L</kwd><kwd>adenovirus</kwd></kwd-group><funding-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">King Abdulaziz City for Science and Technology</named-content><named-content content-type="funder-identifier">10.13039/501100004919</named-content></funding-source><award-id>AT-35–171</award-id></award-group></funding-group><counts><page-count count="10"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Arabie saoudite</li><li>Canada</li></country><region><li>Ontario</li></region></list><tree><noCountry><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name></noCountry><country name="Arabie saoudite"><noRegion><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M" last="Hashem">Anwar M. Hashem</name></noRegion><name sortKey="Al Amri, Sawsan S" sort="Al Amri, Sawsan S" uniqKey="Al Amri S" first="Sawsan S" last="Al-Amri">Sawsan S. Al-Amri</name><name sortKey="Al Amri, Sawsan S" sort="Al Amri, Sawsan S" uniqKey="Al Amri S" first="Sawsan S" last="Al-Amri">Sawsan S. Al-Amri</name><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y" last="Alhabbab">Rowa Y. Alhabbab</name><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y" last="Alhabbab">Rowa Y. Alhabbab</name><name sortKey="Alharbi, Naif Khalaf" sort="Alharbi, Naif Khalaf" uniqKey="Alharbi N" first="Naif Khalaf" last="Alharbi">Naif Khalaf Alharbi</name><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M" last="Hashem">Anwar M. Hashem</name><name sortKey="S Almasoud, Abdulrahman" sort="S Almasoud, Abdulrahman" uniqKey="S Almasoud A" first="Abdulrahman" last="S. Almasoud">Abdulrahman S. Almasoud</name><name sortKey="Sohrab, Sayed S" sort="Sohrab, Sayed S" uniqKey="Sohrab S" first="Sayed S" last="Sohrab">Sayed S. Sohrab</name></country><country name="Canada"><region name="Ontario"><name sortKey="Russell, Marsha" sort="Russell, Marsha" uniqKey="Russell M" first="Marsha" last="Russell">Marsha Russell</name></region><name sortKey="Li, Xuguang" sort="Li, Xuguang" uniqKey="Li X" first="Xuguang" last="Li">Xuguang Li</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|clé= PMC:7107499
|texte= A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:30911758" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |