Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
Identifieur interne : 000344 ( Main/Exploration ); précédent : 000343; suivant : 000345Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
Auteurs : Madhusudan Rajendran [États-Unis] ; Raffael Nachbagauer [États-Unis] ; Megan E. Ermler [États-Unis] ; Paul Bunduc [États-Unis] ; Fatima Amanat [États-Unis] ; Ruvim Izikson [États-Unis] ; Manon Cox [États-Unis] ; Peter Palese [États-Unis] ; Maryna Eichelberger [États-Unis] ; Florian Krammer [États-Unis]Source :
- mBio [ 2150-7511 ] ; 2017.
Abstract
Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed. It appears that antibody levels against N1 neuraminidases were lower than those against N2 or B neuraminidases. The anti-neuraminidase antibody levels increased with age and were, in general, highest against strains that circulated during the childhood of the tested individuals, providing evidence for “original antigenic sin.” Titers measured by ELISA correlated well with titers measured by the neuraminidase inhibition assays. However, in the case of the 2009 pandemic H1N1 virus, we found evidence of interference from antibodies binding to the conserved stalk domain of the hemagglutinin. In conclusion, we found that antibodies against the neuraminidase differ in magnitude and breadth between subtypes and age groups in the human population. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.)
Url:
DOI: 10.1128/mBio.02281-16
PubMed: 28325769
PubMed Central: 5362038
Affiliations:
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and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin</title><author><name sortKey="Rajendran, Madhusudan" sort="Rajendran, Madhusudan" uniqKey="Rajendran M" first="Madhusudan" last="Rajendran">Madhusudan Rajendran</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Nachbagauer, Raffael" sort="Nachbagauer, Raffael" uniqKey="Nachbagauer R" first="Raffael" last="Nachbagauer">Raffael Nachbagauer</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ermler, Megan E" sort="Ermler, Megan E" uniqKey="Ermler M" first="Megan E." last="Ermler">Megan E. Ermler</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Bunduc, Paul" sort="Bunduc, Paul" uniqKey="Bunduc P" first="Paul" last="Bunduc">Paul Bunduc</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Amanat, Fatima" sort="Amanat, Fatima" uniqKey="Amanat F" first="Fatima" last="Amanat">Fatima Amanat</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Izikson, Ruvim" sort="Izikson, Ruvim" uniqKey="Izikson R" first="Ruvim" last="Izikson">Ruvim Izikson</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Protein Sciences Corp., Meriden, Connecticut, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Sciences Corp., Meriden, Connecticut</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Cox, Manon" sort="Cox, Manon" uniqKey="Cox M" first="Manon" last="Cox">Manon Cox</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Protein Sciences Corp., Meriden, Connecticut, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Sciences Corp., Meriden, Connecticut</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Eichelberger, Maryna" sort="Eichelberger, Maryna" uniqKey="Eichelberger M" first="Maryna" last="Eichelberger">Maryna Eichelberger</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed. It appears that antibody levels against N1 neuraminidases were lower than those against N2 or B neuraminidases. The anti-neuraminidase antibody levels increased with age and were, in general, highest against strains that circulated during the childhood of the tested individuals, providing evidence for “original antigenic sin.” Titers measured by ELISA correlated well with titers measured by the neuraminidase inhibition assays. However, in the case of the 2009 pandemic H1N1 virus, we found evidence of interference from antibodies binding to the conserved stalk domain of the hemagglutinin. In conclusion, we found that antibodies against the neuraminidase differ in magnitude and breadth between subtypes and age groups in the human population. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.)</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Krammer, F" uniqKey="Krammer F">F Krammer</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heaton, Ns" uniqKey="Heaton N">NS Heaton</name></author><author><name sortKey="Sachs, D" uniqKey="Sachs D">D Sachs</name></author><author><name sortKey="Chen, Cj" uniqKey="Chen C">CJ Chen</name></author><author><name sortKey="Hai, R" uniqKey="Hai R">R Hai</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wohlbold, Tj" uniqKey="Wohlbold T">TJ Wohlbold</name></author><author><name sortKey="Krammer, F" uniqKey="Krammer F">F Krammer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eichelberger, Mc" uniqKey="Eichelberger M">MC Eichelberger</name></author><author><name sortKey="Wan, H" uniqKey="Wan H">H Wan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansson, Be" uniqKey="Johansson B">BE Johansson</name></author><author><name sortKey="Matthews, Jt" uniqKey="Matthews J">JT Matthews</name></author><author><name sortKey="Kilbourne, Ed" uniqKey="Kilbourne E">ED Kilbourne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wohlbold, Tj" uniqKey="Wohlbold T">TJ Wohlbold</name></author><author><name sortKey="Nachbagauer, R" uniqKey="Nachbagauer R">R Nachbagauer</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name></author><author><name sortKey="Tan, Gs" uniqKey="Tan G">GS Tan</name></author><author><name sortKey="Hirsh, A" uniqKey="Hirsh A">A Hirsh</name></author><author><name sortKey="Brokstad, Ka" uniqKey="Brokstad K">KA Brokstad</name></author><author><name sortKey="Cox, Rj" uniqKey="Cox R">RJ 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Al" uniqKey="Meyer A">AL Meyer</name></author><author><name sortKey="Patriarca, Pa" uniqKey="Patriarca P">PA Patriarca</name></author><author><name sortKey="Cox, Mm" uniqKey="Cox M">MM Cox</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Maryland</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Rajendran, Madhusudan" sort="Rajendran, Madhusudan" uniqKey="Rajendran M" first="Madhusudan" last="Rajendran">Madhusudan Rajendran</name></region><name sortKey="Amanat, Fatima" sort="Amanat, Fatima" uniqKey="Amanat F" first="Fatima" last="Amanat">Fatima Amanat</name><name sortKey="Bunduc, Paul" sort="Bunduc, Paul" uniqKey="Bunduc P" first="Paul" last="Bunduc">Paul Bunduc</name><name sortKey="Cox, Manon" sort="Cox, Manon" uniqKey="Cox M" first="Manon" last="Cox">Manon Cox</name><name sortKey="Eichelberger, Maryna" sort="Eichelberger, Maryna" uniqKey="Eichelberger M" first="Maryna" last="Eichelberger">Maryna Eichelberger</name><name sortKey="Ermler, Megan E" sort="Ermler, Megan E" uniqKey="Ermler M" first="Megan E." last="Ermler">Megan E. Ermler</name><name sortKey="Izikson, Ruvim" sort="Izikson, Ruvim" uniqKey="Izikson R" first="Ruvim" last="Izikson">Ruvim Izikson</name><name sortKey="Krammer, Florian" sort="Krammer, Florian" uniqKey="Krammer F" first="Florian" last="Krammer">Florian Krammer</name><name sortKey="Nachbagauer, Raffael" sort="Nachbagauer, Raffael" uniqKey="Nachbagauer R" first="Raffael" last="Nachbagauer">Raffael Nachbagauer</name><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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