Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans
Identifieur interne : 001386 ( Main/Exploration ); précédent : 001385; suivant : 001387Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans
Auteurs : Matthew R. Sandbulte [États-Unis] ; Gretchen S. Jimenez [États-Unis] ; Adrianus C. M. Boon [États-Unis] ; Larry R. Smith [États-Unis] ; John J. Treanor [États-Unis] ; Richard J. Webby [États-Unis]Source :
- PLoS Medicine [ 1549-1277 ] ; 2007.
Abstract
A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA) of H5N1 viruses (avN1) and of endemic human H1N1 viruses (huN1) are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection.
Mice were immunized against the NA of a contemporary human H1N1 strain by DNA vaccination. They were challenged with recombinant A/Puerto Rico/8/34 (PR8) viruses bearing huN1 (PR8-huN1) or avN1 (PR8-avN1) or with H5N1 virus A/Vietnam/1203/04. Additional naïve mice were injected with sera from vaccinated mice prior to H5N1 challenge. Also, serum specimens from humans were analyzed for reactivity with avN1. Immunization elicited a serum IgG response to huN1 and robust protection against the homologous challenge virus. Immunized mice were partially protected from lethal challenge with H5N1 virus or recombinant PR8-avN1. Sera transferred from immunized mice to naïve animals conferred similar protection against H5N1 mortality. Analysis of human sera showed that antibodies able to inhibit the sialidase activity of avN1 exist in some individuals.
These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.
Url:
DOI: 10.1371/journal.pmed.0040059
PubMed: 17298168
PubMed Central: 1796909
Affiliations:
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Boon</name><affiliation wicri:level="2"><nlm:aff id="aff1"> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Smith, Larry R" sort="Smith, Larry R" uniqKey="Smith L" first="Larry R" last="Smith">Larry R. 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Sandbulte</name><affiliation wicri:level="2"><nlm:aff id="aff1"> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Jimenez, Gretchen S" sort="Jimenez, Gretchen S" uniqKey="Jimenez G" first="Gretchen S" last="Jimenez">Gretchen S. Jimenez</name><affiliation wicri:level="2"><nlm:aff id="aff2"> Vical, San Diego, California, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vical, San Diego, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Boon, Adrianus C M" sort="Boon, Adrianus C M" uniqKey="Boon A" first="Adrianus C. M" last="Boon">Adrianus C. M. Boon</name><affiliation wicri:level="2"><nlm:aff id="aff1"> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Smith, Larry R" sort="Smith, Larry R" uniqKey="Smith L" first="Larry R" last="Smith">Larry R. Smith</name><affiliation wicri:level="2"><nlm:aff id="aff2"> Vical, San Diego, California, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vical, San Diego, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Treanor, John J" sort="Treanor, John J" uniqKey="Treanor J" first="John J" last="Treanor">John J. Treanor</name><affiliation wicri:level="2"><nlm:aff id="aff3"> Infectious Diseases Unit, University of Rochester, Rochester, New York, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Infectious Diseases Unit, University of Rochester, Rochester, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J" last="Webby">Richard J. Webby</name><affiliation wicri:level="2"><nlm:aff id="aff1"> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Medicine</title><idno type="ISSN">1549-1277</idno><idno type="eISSN">1549-1676</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="st1"><title>Background</title><p>A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA) of H5N1 viruses (avN1) and of endemic human H1N1 viruses (huN1) are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection.</p></sec><sec id="st2"><title>Methods and Findings</title><p>Mice were immunized against the NA of a contemporary human H1N1 strain by DNA vaccination. They were challenged with recombinant A/Puerto Rico/8/34 (PR8) viruses bearing huN1 (PR8-huN1) or avN1 (PR8-avN1) or with H5N1 virus A/Vietnam/1203/04. Additional naïve mice were injected with sera from vaccinated mice prior to H5N1 challenge. Also, serum specimens from humans were analyzed for reactivity with avN1. Immunization elicited a serum IgG response to huN1 and robust protection against the homologous challenge virus. Immunized mice were partially protected from lethal challenge with H5N1 virus or recombinant PR8-avN1. Sera transferred from immunized mice to naïve animals conferred similar protection against H5N1 mortality. Analysis of human sera showed that antibodies able to inhibit the sialidase activity of avN1 exist in some individuals.</p></sec><sec id="st3"><title>Conclusions</title><p>These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wong, Ss" uniqKey="Wong S">SS Wong</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kida, H" uniqKey="Kida H">H Kida</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Yanagawa, R" uniqKey="Yanagawa R">R Yanagawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoden, S" uniqKey="Yoden S">S Yoden</name></author><author><name sortKey="Kida, H" uniqKey="Kida H">H Kida</name></author><author><name sortKey="Kuwabara, M" uniqKey="Kuwabara M">M 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Grais</name></author><author><name sortKey="Lafont, Ba" uniqKey="Lafont B">BA Lafont</name></author><author><name sortKey="Miller, Ma" uniqKey="Miller M">MA Miller</name></author><author><name sortKey="Simonsen, L" uniqKey="Simonsen L">L Simonsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilbourne, Ed" uniqKey="Kilbourne E">ED Kilbourne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Monto, As" uniqKey="Monto A">AS Monto</name></author><author><name sortKey="Kendal, Ap" uniqKey="Kendal A">AP Kendal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eickhoff, Tc" uniqKey="Eickhoff T">TC Eickhoff</name></author><author><name sortKey="Meiklejohn, G" uniqKey="Meiklejohn G">G Meiklejohn</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Tennessee</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Tennessee"><name sortKey="Sandbulte, Matthew R" sort="Sandbulte, Matthew R" uniqKey="Sandbulte M" first="Matthew R" last="Sandbulte">Matthew R. Sandbulte</name></region><name sortKey="Boon, Adrianus C M" sort="Boon, Adrianus C M" uniqKey="Boon A" first="Adrianus C. M" last="Boon">Adrianus C. M. Boon</name><name sortKey="Jimenez, Gretchen S" sort="Jimenez, Gretchen S" uniqKey="Jimenez G" first="Gretchen S" last="Jimenez">Gretchen S. Jimenez</name><name sortKey="Smith, Larry R" sort="Smith, Larry R" uniqKey="Smith L" first="Larry R" last="Smith">Larry R. Smith</name><name sortKey="Treanor, John J" sort="Treanor, John J" uniqKey="Treanor J" first="John J" last="Treanor">John J. Treanor</name><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J" last="Webby">Richard J. Webby</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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