NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets
Identifieur interne : 000E50 ( Main/Exploration ); précédent : 000E49; suivant : 000E51NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets
Auteurs : Bin Zhou [États-Unis] ; Yan Li [États-Unis, République populaire de Chine] ; Jessica A. Belser ; Melissa B. Pearce ; Mirco Schmolke [États-Unis] ; Anju X. Subba [États-Unis] ; Zhengli Shi [République populaire de Chine] ; Sherif R. Zaki [Géorgie (pays)] ; Dianna M. Blau [Géorgie (pays)] ; Adolfo García-Sastre [États-Unis] ; Terrence M. Tumpey ; David E. Wentworth [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 2010.
Abstract
Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.
Url:
DOI: 10.1016/j.vaccine.2010.08.106
PubMed: 20934458
PubMed Central: 2991506
Affiliations:
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Pearce</name><affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff><wicri:noCountry code="subfield">NCIRD</wicri:noCountry></affiliation></author><author><name sortKey="Schmolke, Mirco" sort="Schmolke, Mirco" uniqKey="Schmolke M" first="Mirco" last="Schmolke">Mirco Schmolke</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Microbiology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Subba, Anju X" sort="Subba, Anju X" uniqKey="Subba A" first="Anju X." last="Subba">Anju X. 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Blau</name><affiliation wicri:level="1"><nlm:aff id="A6">Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea><wicri:noRegion>Atlanta</wicri:noRegion></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Microbiology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A7">Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A8">Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name><affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff><wicri:noCountry code="subfield">NCIRD</wicri:noCountry></affiliation></author><author><name sortKey="Wentworth, David E" sort="Wentworth, David E" uniqKey="Wentworth D" first="David E." last="Wentworth">David E. Wentworth</name><affiliation wicri:level="2"><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Wadsworth Center, New York State Department of Health, State University of New York, Albany</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biomedical Sciences, School of Public Health, State University of New York, Albany</wicri:cityArea></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno><idno type="eISSN">1873-2518</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.</p></div></front></TEI><affiliations><list><country><li>Géorgie (pays)</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Hubei</li><li>État de New York</li></region><settlement><li>Wuhan</li></settlement></list><tree><noCountry><name sortKey="Belser, Jessica A" sort="Belser, Jessica A" uniqKey="Belser J" first="Jessica A." last="Belser">Jessica A. Belser</name><name sortKey="Pearce, Melissa B" sort="Pearce, Melissa B" uniqKey="Pearce M" first="Melissa B." last="Pearce">Melissa B. Pearce</name><name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name></noCountry><country name="États-Unis"><region name="État de New York"><name sortKey="Zhou, Bin" sort="Zhou, Bin" uniqKey="Zhou B" first="Bin" last="Zhou">Bin Zhou</name></region><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><name sortKey="Schmolke, Mirco" sort="Schmolke, Mirco" uniqKey="Schmolke M" first="Mirco" last="Schmolke">Mirco Schmolke</name><name sortKey="Subba, Anju X" sort="Subba, Anju X" uniqKey="Subba A" first="Anju X." last="Subba">Anju X. Subba</name><name sortKey="Wentworth, David E" sort="Wentworth, David E" uniqKey="Wentworth D" first="David E." last="Wentworth">David E. Wentworth</name><name sortKey="Wentworth, David E" sort="Wentworth, David E" uniqKey="Wentworth D" first="David E." last="Wentworth">David E. Wentworth</name><name sortKey="Zhou, Bin" sort="Zhou, Bin" uniqKey="Zhou B" first="Bin" last="Zhou">Bin Zhou</name></country><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name></region><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name></country><country name="Géorgie (pays)"><noRegion><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name></noRegion><name sortKey="Blau, Dianna M" sort="Blau, Dianna M" uniqKey="Blau D" first="Dianna M." last="Blau">Dianna M. 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