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Naturally Occurring Antibodies in Humans Can Neutralize a Variety of Influenza Virus Strains, Including H3, H1, H2, and H5 ▿§

Identifieur interne : 000804 ( Pmc/Checkpoint ); précédent : 000803; suivant : 000805

Naturally Occurring Antibodies in Humans Can Neutralize a Variety of Influenza Virus Strains, Including H3, H1, H2, and H5 ▿§

Auteurs : Nobuko Ohshima ; Yoshitaka Iba ; Ritsuko Kubota-Koketsu [Japon] ; Yoshizo Asano [Japon] ; Yoshinobu Okuno [Japon] ; Yoshikazu Kurosawa

Source :

RBID : PMC:3194982

Abstract

Influenza A viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs) are not broadly cross-reactive among HA subtypes. We examined the repertoire of neutralizing Abs against influenza viruses in humans. B lymphocytes were collected from donors by apheresis, and Ab libraries were constructed by using phage-display technology. Anti-HA clones were isolated by screening with H3N2 viruses. Their binding activity was examined, and four kinds of Abs showing broad strain specificity were identified from one donor. Two of the Abs, F045-092 and F026-427, were extensively analyzed. They neutralized not only H3N2 but also H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow cytometry suggested that they have the ability to bind to HA and HA1 artificially expressed on the cell surface. They show hemagglutination inhibition activity and do not compete with C179, an Ab thought to bind to the stalk region. F045-092 competes with Abs that recognize sites A and B for binding to HA. Furthermore, the serine at residue 136 in site A could be a part of the epitope. Thus, it is likely that F045-092 and F026-427 bind to a conserved epitope in the head region formed by HA1. Interestingly, while the VH1-69 gene can encode MAbs against the HA stem that are group 1 specific, F045-092 and its relatives that recognize the head region also use VH1-69. The possible epitope recognized by these clones is discussed.


Url:
DOI: 10.1128/JVI.05397-11
PubMed: 21865387
PubMed Central: 3194982


Affiliations:


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<p>Influenza A viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs) are not broadly cross-reactive among HA subtypes. We examined the repertoire of neutralizing Abs against influenza viruses in humans. B lymphocytes were collected from donors by apheresis, and Ab libraries were constructed by using phage-display technology. Anti-HA clones were isolated by screening with H3N2 viruses. Their binding activity was examined, and four kinds of Abs showing broad strain specificity were identified from one donor. Two of the Abs, F045-092 and F026-427, were extensively analyzed. They neutralized not only H3N2 but also H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow cytometry suggested that they have the ability to bind to HA and HA1 artificially expressed on the cell surface. They show hemagglutination inhibition activity and do not compete with C179, an Ab thought to bind to the stalk region. F045-092 competes with Abs that recognize sites A and B for binding to HA. Furthermore, the serine at residue 136 in site A could be a part of the epitope. Thus, it is likely that F045-092 and F026-427 bind to a conserved epitope in the head region formed by HA1. Interestingly, while the
<italic>V
<sub>H</sub>
1</italic>
-
<italic>69</italic>
gene can encode MAbs against the HA stem that are group 1 specific, F045-092 and its relatives that recognize the head region also use
<italic>V
<sub>H</sub>
1</italic>
-
<italic>69</italic>
. The possible epitope recognized by these clones is discussed.</p>
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<article-title>Naturally Occurring Antibodies in Humans Can Neutralize a Variety of Influenza Virus Strains, Including H3, H1, H2, and H5
<xref ref-type="fn" rid="FN3">
<sup></sup>
</xref>
<xref ref-type="fn" rid="FN4">§</xref>
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<name>
<surname>Ohshima</surname>
<given-names>Nobuko</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
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<name>
<surname>Iba</surname>
<given-names>Yoshitaka</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="FN1"></xref>
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<contrib contrib-type="author">
<name>
<surname>Kubota-Koketsu</surname>
<given-names>Ritsuko</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
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<contrib contrib-type="author">
<name>
<surname>Asano</surname>
<given-names>Yoshizo</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
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<xref ref-type="author-notes" rid="FN2"></xref>
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<contrib contrib-type="author">
<name>
<surname>Okuno</surname>
<given-names>Yoshinobu</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
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<contrib contrib-type="author">
<name>
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<given-names>Yoshikazu</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
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Division of Antibody Project, Institute for Comprehensive Medical Science</aff>
<aff id="aff3">
<label>3</label>
Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan</aff>
<aff id="aff2">
<label>2</label>
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan</aff>
<aff id="aff4">
<label>4</label>
The Research Foundation for Microbial Diseases, Osaka University, Kannonji, Kagawa 768-0061, Japan</aff>
</contrib-group>
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<corresp id="cor1">
<label>*</label>
Corresponding author. Mailing address:
<addr-line>Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan</addr-line>
. Phone:
<phone>81 962 93 9387</phone>
. Fax:
<fax>81 962 93 8835</fax>
. E-mail:
<email>kurosawa@fujita-hu.ac.jp</email>
.</corresp>
<fn fn-type="equal" id="FN1">
<label></label>
<p>These authors contributed equally to this work.</p>
</fn>
<fn fn-type="present-address" id="FN2">
<label></label>
<p>Present address: Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.</p>
</fn>
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<pub-date pub-type="ppub">
<month>11</month>
<year>2011</year>
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<month>11</month>
<year>2011</year>
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<volume>85</volume>
<issue>21</issue>
<fpage>11048</fpage>
<lpage>11057</lpage>
<history>
<date date-type="received">
<day>14</day>
<month>6</month>
<year>2011</year>
</date>
<date date-type="accepted">
<day>5</day>
<month>8</month>
<year>2011</year>
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</history>
<permissions>
<copyright-statement>Copyright © 2011, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2011</copyright-year>
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<abstract>
<p>Influenza A viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs) are not broadly cross-reactive among HA subtypes. We examined the repertoire of neutralizing Abs against influenza viruses in humans. B lymphocytes were collected from donors by apheresis, and Ab libraries were constructed by using phage-display technology. Anti-HA clones were isolated by screening with H3N2 viruses. Their binding activity was examined, and four kinds of Abs showing broad strain specificity were identified from one donor. Two of the Abs, F045-092 and F026-427, were extensively analyzed. They neutralized not only H3N2 but also H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow cytometry suggested that they have the ability to bind to HA and HA1 artificially expressed on the cell surface. They show hemagglutination inhibition activity and do not compete with C179, an Ab thought to bind to the stalk region. F045-092 competes with Abs that recognize sites A and B for binding to HA. Furthermore, the serine at residue 136 in site A could be a part of the epitope. Thus, it is likely that F045-092 and F026-427 bind to a conserved epitope in the head region formed by HA1. Interestingly, while the
<italic>V
<sub>H</sub>
1</italic>
-
<italic>69</italic>
gene can encode MAbs against the HA stem that are group 1 specific, F045-092 and its relatives that recognize the head region also use
<italic>V
<sub>H</sub>
1</italic>
-
<italic>69</italic>
. The possible epitope recognized by these clones is discussed.</p>
</abstract>
</article-meta>
</front>
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<name sortKey="Ohshima, Nobuko" sort="Ohshima, Nobuko" uniqKey="Ohshima N" first="Nobuko" last="Ohshima">Nobuko Ohshima</name>
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<name sortKey="Kubota Koketsu, Ritsuko" sort="Kubota Koketsu, Ritsuko" uniqKey="Kubota Koketsu R" first="Ritsuko" last="Kubota-Koketsu">Ritsuko Kubota-Koketsu</name>
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<name sortKey="Asano, Yoshizo" sort="Asano, Yoshizo" uniqKey="Asano Y" first="Yoshizo" last="Asano">Yoshizo Asano</name>
<name sortKey="Okuno, Yoshinobu" sort="Okuno, Yoshinobu" uniqKey="Okuno Y" first="Yoshinobu" last="Okuno">Yoshinobu Okuno</name>
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