A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice
Identifieur interne : 000738 ( Main/Exploration ); précédent : 000737; suivant : 000739A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice
Auteurs : Mahmoud M. Shehata ; Ahmed Kandeil ; Ahmed Mostafa ; Sara H. Mahmoud ; Mokhtar R. Gomaa ; Rabeh El-Shesheny ; Richard Webby ; Ghazi Kayali [États-Unis, Liban] ; Mohamed A. AliSource :
- Pathogens [ 2076-0817 ] ; 2019.
Abstract
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736–761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses.
Url:
DOI: 10.3390/pathogens8040281
PubMed: 31810359
PubMed Central: 6963271
Affiliations:
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Shehata</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Kandeil, Ahmed" sort="Kandeil, Ahmed" uniqKey="Kandeil A" first="Ahmed" last="Kandeil">Ahmed Kandeil</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Mahmoud, Sara H" sort="Mahmoud, Sara H" uniqKey="Mahmoud S" first="Sara H." last="Mahmoud">Sara H. 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Gomaa</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="El Shesheny, Rabeh" sort="El Shesheny, Rabeh" uniqKey="El Shesheny R" first="Rabeh" last="El-Shesheny">Rabeh El-Shesheny</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pathogens-08-00281">Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;<email>richard.webby@stjude.org</email></nlm:aff></affiliation></author><author><name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name><affiliation><nlm:aff id="af2-pathogens-08-00281">Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;<email>richard.webby@stjude.org</email></nlm:aff></affiliation></author><author><name sortKey="Kayali, Ghazi" sort="Kayali, Ghazi" uniqKey="Kayali G" first="Ghazi" last="Kayali">Ghazi Kayali</name><affiliation wicri:level="2"><nlm:aff id="af3-pathogens-08-00281">Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-pathogens-08-00281">Human Link, Baabda 1109, Lebanon</nlm:aff><country xml:lang="fr">Liban</country><wicri:regionArea>Human Link, Baabda 1109</wicri:regionArea><wicri:noRegion>Baabda 1109</wicri:noRegion></affiliation></author><author><name sortKey="A Ali, Mohamed" sort="A Ali, Mohamed" uniqKey="A Ali M" first="Mohamed" last="A. 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Ali</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31810359</idno><idno type="pmc">6963271</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963271</idno><idno type="RBID">PMC:6963271</idno><idno type="doi">10.3390/pathogens8040281</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001116</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001116</idno><idno type="wicri:Area/Pmc/Curation">001116</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001116</idno><idno type="wicri:Area/Pmc/Checkpoint">000431</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000431</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:31810359</idno><idno type="wicri:Area/PubMed/Corpus">000341</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000341</idno><idno type="wicri:Area/PubMed/Curation">000341</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000341</idno><idno type="wicri:Area/PubMed/Checkpoint">000703</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000703</idno><idno type="wicri:Area/Ncbi/Merge">002423</idno><idno type="wicri:Area/Ncbi/Curation">002423</idno><idno type="wicri:Area/Ncbi/Checkpoint">002423</idno><idno type="wicri:Area/Main/Merge">000741</idno><idno type="wicri:Area/Main/Curation">000738</idno><idno type="wicri:Area/Main/Exploration">000738</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice</title><author><name sortKey="Shehata, Mahmoud M" sort="Shehata, Mahmoud M" uniqKey="Shehata M" first="Mahmoud M." last="Shehata">Mahmoud M. Shehata</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Kandeil, Ahmed" sort="Kandeil, Ahmed" uniqKey="Kandeil A" first="Ahmed" last="Kandeil">Ahmed Kandeil</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Mahmoud, Sara H" sort="Mahmoud, Sara H" uniqKey="Mahmoud S" first="Sara H." last="Mahmoud">Sara H. Mahmoud</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Gomaa, Mokhtar R" sort="Gomaa, Mokhtar R" uniqKey="Gomaa M" first="Mokhtar R." last="Gomaa">Mokhtar R. Gomaa</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="El Shesheny, Rabeh" sort="El Shesheny, Rabeh" uniqKey="El Shesheny R" first="Rabeh" last="El-Shesheny">Rabeh El-Shesheny</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pathogens-08-00281">Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;<email>richard.webby@stjude.org</email></nlm:aff></affiliation></author><author><name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name><affiliation><nlm:aff id="af2-pathogens-08-00281">Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;<email>richard.webby@stjude.org</email></nlm:aff></affiliation></author><author><name sortKey="Kayali, Ghazi" sort="Kayali, Ghazi" uniqKey="Kayali G" first="Ghazi" last="Kayali">Ghazi Kayali</name><affiliation wicri:level="2"><nlm:aff id="af3-pathogens-08-00281">Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-pathogens-08-00281">Human Link, Baabda 1109, Lebanon</nlm:aff><country xml:lang="fr">Liban</country><wicri:regionArea>Human Link, Baabda 1109</wicri:regionArea><wicri:noRegion>Baabda 1109</wicri:noRegion></affiliation></author><author><name sortKey="A Ali, Mohamed" sort="A Ali, Mohamed" uniqKey="A Ali M" first="Mohamed" last="A. Ali">Mohamed A. Ali</name><affiliation><nlm:aff id="af1-pathogens-08-00281">Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt;<email>Mahmoud.Shehata@human-link.org</email> (M.M.S.);<email>ahmed.Kandeil@human-link.org</email> (A.K.);<email>ahmed_elsayed@daad-alumni.de</email> (A.M.);<email>sarahussein9@yahoo.com</email> (S.H.M.);<email>Mokhtar.Rizk@human-link.org</email> (M.R.G.);<email>rabeh.elshesheny@stjude.org</email> (R.E.-S.)</nlm:aff></affiliation></author></analytic><series><title level="j">Pathogens</title><idno type="eISSN">2076-0817</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736–761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses. </p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. 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Mahmoud</name><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><name sortKey="Shehata, Mahmoud M" sort="Shehata, Mahmoud M" uniqKey="Shehata M" first="Mahmoud M." last="Shehata">Mahmoud M. Shehata</name><name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name></noCountry><country name="États-Unis"><region name="Texas"><name sortKey="Kayali, Ghazi" sort="Kayali, Ghazi" uniqKey="Kayali G" first="Ghazi" last="Kayali">Ghazi Kayali</name></region></country><country name="Liban"><noRegion><name sortKey="Kayali, Ghazi" sort="Kayali, Ghazi" uniqKey="Kayali G" first="Ghazi" last="Kayali">Ghazi Kayali</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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