Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets
Identifieur interne : 000C52 ( Pmc/Checkpoint ); précédent : 000C51; suivant : 000C53Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets
Auteurs : Surender Khurana [États-Unis] ; Amorsolo L. Suguitan [États-Unis] ; Yonaira Rivera [États-Unis] ; Cameron P. Simmons [Viêt Nam] ; Antonio Lanzavecchia [Suisse] ; Federica Sallusto [Suisse] ; Jody Manischewitz [États-Unis] ; Lisa R. King [États-Unis] ; Kanta Subbarao [États-Unis] ; Hana Golding [États-Unis]Source :
- PLoS Medicine [ 1549-1277 ] ; 2009.
Abstract
Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.
Url:
DOI: 10.1371/journal.pmed.1000049
PubMed: 19381279
PubMed Central: 2661249
Affiliations:
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PMC:2661249Le document en format XML
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King</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Golding, Hana" sort="Golding, Hana" uniqKey="Golding H" first="Hana" last="Golding">Hana Golding</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19381279</idno><idno type="pmc">2661249</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661249</idno><idno type="RBID">PMC:2661249</idno><idno type="doi">10.1371/journal.pmed.1000049</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000C21</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C21</idno><idno type="wicri:Area/Pmc/Curation">000C21</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C21</idno><idno type="wicri:Area/Pmc/Checkpoint">000C52</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C52</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets</title><author><name sortKey="Khurana, Surender" sort="Khurana, Surender" uniqKey="Khurana S" first="Surender" last="Khurana">Surender Khurana</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Suguitan, Amorsolo L" sort="Suguitan, Amorsolo L" uniqKey="Suguitan A" first="Amorsolo L." last="Suguitan">Amorsolo L. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Med</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Med</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosmed</journal-id><journal-title-group><journal-title>PLoS Medicine</journal-title></journal-title-group><issn pub-type="ppub">1549-1277</issn><issn pub-type="epub">1549-1676</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19381279</article-id><article-id pub-id-type="pmc">2661249</article-id><article-id pub-id-type="publisher-id">08-PLME-RA-3189R2</article-id><article-id pub-id-type="doi">10.1371/journal.pmed.1000049</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Infectious Diseases</subject><subject>Infectious Diseases/Respiratory Infections</subject><subject>Infectious Diseases/Viral Infections</subject></subj-group></article-categories><title-group><article-title>Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets</article-title><alt-title alt-title-type="running-head">Epitope Profile in H5N1 Survivors</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Khurana</surname><given-names>Surender</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Suguitan</surname><given-names>Amorsolo L.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rivera</surname><given-names>Yonaira</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Simmons</surname><given-names>Cameron P.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lanzavecchia</surname><given-names>Antonio</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sallusto</surname><given-names>Federica</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Manischewitz</surname><given-names>Jody</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>King</surname><given-names>Lisa R.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Subbarao</surname><given-names>Kanta</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Golding</surname><given-names>Hana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Institute for Research in Biomedicine, Bellinzona, Switzerland</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Peiris</surname><given-names>Malik</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">The University of Hong Kong, Hong Kong</aff><author-notes><corresp id="cor1">* E-mail: <email>hana.golding@fda.hhs.gov</email></corresp><fn fn-type="con"><p><ext-link ext-link-type="uri" xlink:href="http://www.icmje.org/">ICMJE</ext-link> criteria for authorship read and met: SK ALS YR CPS AL FS JM LRK KS HG. Agree with the manuscript’s results and conclusions: SK ALS YR CPS AL FS JM LRK KS HG. Designed the experiments/the study: SK CPS KS HG. Analyzed the data: SK ALS YR CPS HG. Collected data/did experiments for the study: SK ALS YR JM LRK. Wrote the first draft of the paper: SK HG. Contributed to the writing of the paper: SK ALS CPS AL KS HG. Conducted virus neutralization assays involving H5N1 wild-type virus and performed preliminary work on evaluating the efficiency of synthetic peptides to block the neutralizing activity of H5 HA-specific hMAbs: ALS. Provided reagents: AL. Supervised the work done at IRB and provided human monoclonal antibodies: FS. Performed the microneutralization assay and analyzed the data from the assays: JM LRK. Designed some of the experiments: KS.</p></fn></author-notes><pub-date pub-type="collection"><month>4</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>21</day><month>4</month><year>2009</year></pub-date><volume>6</volume><issue>4</issue><elocation-id>e1000049</elocation-id><history><date date-type="received"><day>17</day><month>11</month><year>2008</year></date><date date-type="accepted"><day>12</day><month>2</month><year>2009</year></date></history><permissions><copyright-statement>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</copyright-statement><copyright-year>2009</copyright-year><license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</license-p></license></permissions><related-article id="RA1" related-article-type="companion" vol="6" page="e1000064" ext-link-type="pmc"><pmc-comment>related-article was converted to @ext-link-type="pmc" and original @xlink:href value
was info:doi/10.1371/journal.pmed.1000064</pmc-comment>
<article-title>Mapping antibody epitopes of the avian H5N1 influenza virus</article-title></related-article><abstract abstract-type="toc"><p>Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.</p></abstract><abstract><sec><title>Background</title><p>Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protective immune responses against avian influenza. Characterizing the B cell responses in convalescent individuals could help in the design of future vaccines and therapeutics.</p></sec><sec><title>Methods and Findings</title><p>To address this need, we generated whole-genome–fragment phage display libraries (GFPDL) expressing fragments of 15–350 amino acids covering all the proteins of A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection. This approach led to the mapping of two broadly neutralizing human monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2 ectodomain. In addition, for the first time to our knowledge in humans, we identified strong reactivity against PB1-F2, a putative virulence factor, following H5N1 infection. Importantly, novel epitopes were identified, which were recognized by H5N1-convalescent sera but did not react with sera from control individuals (H5N1 naïve, H1N1 or H3N2 seropositive).</p></sec><sec><title>Conclusion</title><p>This is the first study, to our knowledge, describing the complete antibody repertoire following H5N1 infection. Collectively, these data will contribute to rational vaccine design and new H5N1-specific serodiagnostic surveillance tools.</p></sec></abstract><abstract abstract-type="editor"><title>Editors' Summary</title><sec id="s5a"><title></title><sec id="s5a1"><title>Background</title><p>Every winter, millions of people catch influenza, a viral infection of the airways. Most recover quickly but seasonal influenza outbreaks (epidemics) kill about half a million people annually. These epidemics occur because small but frequent changes in the viral proteins (antigens) to which the human immune system responds mean that an immune response produced one year by infection or through vaccination provides only partial protection against influenza the next year. Influenza viruses also occasionally appear that contain major antigenic changes. Human populations have little or no immunity to such viruses (which often originate in animals or birds), so they can start deadly global epidemics (pandemics ). Worryingly, the last influenza pandemic occurred in 1968 and many experts fear that another pandemic is now overdue. The trigger for such a pandemic, they think, could be the avian (bird) H5N1 influenza virus, which first appeared in 1996 in a goose in China. The name indicates the types of two major influenza antigens present in the virus: H5N1 carries type 5 hemagglutinin and type 1 neuraminidase.</p></sec><sec id="s5a2"><title>Why Was This Study Done?</title><p>H5N1 has caused about 400 confirmed cases of human influenza and more than 250 deaths in the past decade but it has not started a human pandemic because it cannot pass easily between people. However, it could possibly acquire this ability at any time, so it is a priority to develop both vaccines that will provide protection against a pandemic H5N1 viral strain, as well as antibody-based antiviral therapies for people not protected by vaccination (antibodies are proteins produced by the immune system that help to fight infections; people can sometimes be protected from infection by injecting them with pre-prepared antibodies). To do this, scientists need to know how the human immune system responds to the H5N1 virus. In particular, they need to know which parts of the virus the immune system can detect and make antibodies against. In this study, therefore, the researchers characterize the specific antibody responses found in people recovering from infection with H5N1.</p></sec><sec id="s5a3"><title>What Did the Researchers Do and Find?</title><p>The researchers made several “genome-fragment phage display libraries”, collections of bacterial viruses (phages) engineered so that each phage makes one of many possible short pieces (polypeptides) of a nonphage protein. Such “libraries” can be used to investigate which fragments are recognized by antibodies from a given source. In this case, several libraries were made that contained fragments of the genome of the H5N1 strain responsible for an outbreak of human influenza in Vietnam in 2004–2005 (A/Vietnam/1203/2004). The researchers used these libraries to analyze the antibodies made by five Vietnamese people recovering from infection with A/Vietnam/1203/2004. H5N1 convalescent blood samples, the researchers report, contained antibodies that recognized small regions (“epitopes”) in several viral proteins, including hemagglutinin, neuraminidase, a structural protein called M2, and a viral protein called PB1-F2 that is partly responsible for the severity of H5N1 infections. Several of the novel epitopes identified were not recognized by antibodies in blood taken from people recovering from infection with other influenza viruses. The researchers also used their phage display libraries to analyze two neutralizing human monoclonal antibodies generated from patients infected with A/Vietnam/1203/2004 (neutralizing antibodies protect mice against normally lethal challenge with H5N1; monoclonal antibodies are generated in the laboratory by creating continuously growing cell lines that produce a single type of antibody). Importantly, both of the neutralizing monoclonal antibodies recognized “noncontinuous conformation-dependent epitopes”—protein sequences that are not adjacent to one another in the polypeptide sequence of the protein, but that lie close together in space because of the way the protein is folded up.</p></sec><sec id="s5a4"><title>What Do These Findings Mean?</title><p>Although some aspects of the antibody repertoire produced in people exposed to the H5N1 influenza virus may have been missed in this analysis, these findings provide important and detailed new information about how the human immune system responds to infection with this virus. In particular, they show that people recovering from H5N1 infection make a diverse range of antibodies against several viral proteins for at least six months and identify specific parts of H5N1 that may be particularly good at stimulating a protective immune response. This information can now be used to help design vaccines against H5N1 and antibody-based therapies for the treatment of H5N1 infections, and to develop new tools for monitoring outbreaks of avian influenza in human populations.</p></sec><sec id="s5a5"><title>Additional Information</title><p>Please access these Web sites via the online version of this summary at <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1371/journal.pmed.1000049">http://dx.doi.org/10.1371/journal.pmed.1000049</ext-link>.</p><list list-type="bullet"><list-item><p>This study is further discussed in a <italic>PLoS Medicine</italic><ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1371/journal.pmed.1000064">Perspective by Malik Peiris</ext-link></p></list-item><list-item><p>The US Centers for Disease Control and Prevention provides information for about <ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/flu">influenza</ext-link> for patients and professionals, including specific information on <ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/flu/avian/index.htm">avian</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://www.pandemicflu.gov/index.html">pandemic</ext-link> influenza (in several languages)</p></list-item><list-item><p>The World Health Organization provides information on <ext-link ext-link-type="uri" xlink:href="http://www.who.int/mediacentre/factsheets/fs211">influenza</ext-link> (in several languages) and on <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/disease/avian_influenza">H5N1 avian influenza</ext-link> (in several languages), and a <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html">global timeline about H5N1 avian influenza infection</ext-link> in birds and people</p></list-item><list-item><p>The <ext-link ext-link-type="uri" xlink:href="http://www.hpa.org.uk/webw/HPAweb%26Page%26HPAwebAutoListName/Page/1202115586990%3Fp%3D1202115586990">UK Health Protection Agency</ext-link> provides information on avian, pandemic, and epidemic (seasonal) influenza</p></list-item><list-item><p>MedlinePlus provides a list of links to other information about <ext-link ext-link-type="uri" xlink:href="http://www.nlm.nih.gov/medlineplus/flu.html">influenza</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://www.nlm.nih.gov/medlineplus/birdflu.html">bird flu</ext-link> (in English and Spanish)</p></list-item></list></sec></sec></abstract><counts><page-count count="13"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Suisse</li><li>Viêt Nam</li><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Khurana, Surender" sort="Khurana, Surender" uniqKey="Khurana S" first="Surender" last="Khurana">Surender Khurana</name></region><name sortKey="Golding, Hana" sort="Golding, Hana" uniqKey="Golding H" first="Hana" last="Golding">Hana Golding</name><name sortKey="King, Lisa R" sort="King, Lisa R" uniqKey="King L" first="Lisa R." last="King">Lisa R. King</name><name sortKey="Manischewitz, Jody" sort="Manischewitz, Jody" uniqKey="Manischewitz J" first="Jody" last="Manischewitz">Jody Manischewitz</name><name sortKey="Rivera, Yonaira" sort="Rivera, Yonaira" uniqKey="Rivera Y" first="Yonaira" last="Rivera">Yonaira Rivera</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Suguitan, Amorsolo L" sort="Suguitan, Amorsolo L" uniqKey="Suguitan A" first="Amorsolo L." last="Suguitan">Amorsolo L. Suguitan</name></country><country name="Viêt Nam"><noRegion><name sortKey="Simmons, Cameron P" sort="Simmons, Cameron P" uniqKey="Simmons C" first="Cameron P." last="Simmons">Cameron P. Simmons</name></noRegion></country><country name="Suisse"><noRegion><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name></noRegion><name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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