Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans
Identifieur interne : 000A61 ( Main/Exploration ); précédent : 000A60; suivant : 000A62Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans
Auteurs : Robert B. Couch [États-Unis] ; William K. Decker [États-Unis] ; Budi Utama [États-Unis] ; Robert L. Atmar [États-Unis] ; Diane Ni O [États-Unis] ; Jing Qi Feng [États-Unis] ; Matthew M. Halpert [États-Unis] ; Gillian M. Air [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.
To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).
Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1∶4 for the H7 vaccine and 1∶661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.
Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.
Url:
DOI: 10.1371/journal.pone.0050830
PubMed: 23239987
PubMed Central: 3519816
Affiliations:
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Couch</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Decker, William K" sort="Decker, William K" uniqKey="Decker W" first="William K." last="Decker">William K. Decker</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Utama, Budi" sort="Utama, Budi" uniqKey="Utama B" first="Budi" last="Utama">Budi Utama</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Atmar, Robert L" sort="Atmar, Robert L" uniqKey="Atmar R" first="Robert L." last="Atmar">Robert L. Atmar</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Ni O, Diane" sort="Ni O, Diane" uniqKey="Ni O D" first="Diane" last="Ni O">Diane Ni O</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Feng, Jing Qi" sort="Feng, Jing Qi" uniqKey="Feng J" first="Jing Qi" last="Feng">Jing Qi Feng</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma</wicri:regionArea><placeName><region type="state">Oklahoma</region></placeName></affiliation></author><author><name sortKey="Halpert, Matthew M" sort="Halpert, Matthew M" uniqKey="Halpert M" first="Matthew M." last="Halpert">Matthew M. Halpert</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Air, Gillian M" sort="Air, Gillian M" uniqKey="Air G" first="Gillian M." last="Air">Gillian M. Air</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma</wicri:regionArea><placeName><region type="state">Oklahoma</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.</p></sec><sec><title>Design</title><p>To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).</p></sec><sec><title>Results</title><p>Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1∶4 for the H7 vaccine and 1∶661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.</p></sec><sec><title>Summary</title><p>Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Schild, Gc" uniqKey="Schild G">GC Schild</name></author><author><name sortKey="Wood, Jm" uniqKey="Wood J">JM Wood</name></author><author><name sortKey="Newman, Rw" uniqKey="Newman R">RW Newman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Treanor, Jj" uniqKey="Treanor J">JJ Treanor</name></author><author><name sortKey="Campbell, Jd" uniqKey="Campbell J">JD Campbell</name></author><author><name sortKey="Zangwill, Km" uniqKey="Zangwill K">KM Zangwill</name></author><author><name sortKey="Rowe, T" uniqKey="Rowe T">T Rowe</name></author><author><name sortKey="Wolff, M" uniqKey="Wolff M">M Wolff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leroux Roels, I" 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R" first="Robert B." last="Couch">Robert B. Couch</name></region><name sortKey="Air, Gillian M" sort="Air, Gillian M" uniqKey="Air G" first="Gillian M." last="Air">Gillian M. Air</name><name sortKey="Atmar, Robert L" sort="Atmar, Robert L" uniqKey="Atmar R" first="Robert L." last="Atmar">Robert L. Atmar</name><name sortKey="Atmar, Robert L" sort="Atmar, Robert L" uniqKey="Atmar R" first="Robert L." last="Atmar">Robert L. Atmar</name><name sortKey="Decker, William K" sort="Decker, William K" uniqKey="Decker W" first="William K." last="Decker">William K. Decker</name><name sortKey="Feng, Jing Qi" sort="Feng, Jing Qi" uniqKey="Feng J" first="Jing Qi" last="Feng">Jing Qi Feng</name><name sortKey="Halpert, Matthew M" sort="Halpert, Matthew M" uniqKey="Halpert M" first="Matthew M." last="Halpert">Matthew M. Halpert</name><name sortKey="Ni O, Diane" sort="Ni O, Diane" uniqKey="Ni O D" first="Diane" last="Ni O">Diane Ni O</name><name sortKey="Utama, Budi" sort="Utama, Budi" uniqKey="Utama B" first="Budi" last="Utama">Budi Utama</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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