Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera
Identifieur interne : 000E81 ( Ncbi/Merge ); précédent : 000E80; suivant : 000E82Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera
Auteurs : Hadi M. Yassine [Qatar] ; Patrick M. Mctamney [États-Unis] ; Jeffery C. Boyington [États-Unis] ; Tracy J. Ruckwardt [États-Unis] ; Michelle C. Crank [États-Unis] ; Maria K. Smatti [Qatar] ; Julie E. Ledgerwood [États-Unis] ; Barney S. Graham [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2018.
Abstract
A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts. Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population. Five group-1 HA SS probes, representing five subtypes, were chosen for this analyses. Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes. Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb. Binding cross-reactivity in sera samples significantly correlated with frequency of H1+H5+ cross-reactive B cells. Interestingly, only 33% of the cross-reactive sera neutralized both H1N1 and H5N1 pseudoviruses. Cross-reactive and neutralizing antibodies were more prevalent in individuals >50 years of age. Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies. Further, a universal vaccine could be designed to boost pre-existing B-cells expressing stem-directed bNAbs.
Url:
DOI: 10.1038/s41598-018-26538-7
PubMed: 29872070
PubMed Central: 5988737
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<front><div type="abstract" xml:lang="en"><p id="Par1">A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts. Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population. Five group-1 HA SS probes, representing five subtypes, were chosen for this analyses. Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes. Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb. Binding cross-reactivity in sera samples significantly correlated with frequency of H1<sup>+</sup>
H5<sup>+</sup>
cross-reactive B cells. Interestingly, only 33% of the cross-reactive sera neutralized both H1N1 and H5N1 pseudoviruses. Cross-reactive and neutralizing antibodies were more prevalent in individuals >50 years of age. Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies. Further, a universal vaccine could be designed to boost pre-existing B-cells expressing stem-directed bNAbs.</p>
</div>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group><journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher><publisher-name>Nature Publishing Group UK</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29872070</article-id>
<article-id pub-id-type="pmc">5988737</article-id>
<article-id pub-id-type="publisher-id">26538</article-id>
<article-id pub-id-type="doi">10.1038/s41598-018-26538-7</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-7592-2788</contrib-id>
<name><surname>Yassine</surname>
<given-names>Hadi M.</given-names>
</name>
<address><email>hyassine@qu.edu.qa</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McTamney</surname>
<given-names>Patrick M.</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boyington</surname>
<given-names>Jeffery C.</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ruckwardt</surname>
<given-names>Tracy J.</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Crank</surname>
<given-names>Michelle C.</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smatti</surname>
<given-names>Maria K.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ledgerwood</surname>
<given-names>Julie E.</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Graham</surname>
<given-names>Barney S.</given-names>
</name>
<address><email>bgraham@mail.nih.gov</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0634 1084</institution-id>
<institution-id institution-id-type="GRID">grid.412603.2</institution-id>
<institution>Qatar University Biomedical Research Center,</institution>
</institution-wrap>
Doha, 2713 Qatar</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.418152.b</institution-id>
<institution>Medimmune,</institution>
</institution-wrap>
Gaithersburg, MD 20878 USA</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution>Vaccine Research Center,</institution>
<institution>National Institute of Allergy and Infectious Diseases,</institution>
</institution-wrap>
Bethesda, MD 20892 USA</aff>
</contrib-group>
<pub-date pub-type="epub"><day>5</day>
<month>6</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>5</day>
<month>6</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="collection"><year>2018</year>
</pub-date>
<volume>8</volume>
<elocation-id>8628</elocation-id>
<history><date date-type="received"><day>5</day>
<month>3</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>11</day>
<month>5</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2018</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p id="Par1">A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts. Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population. Five group-1 HA SS probes, representing five subtypes, were chosen for this analyses. Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes. Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb. Binding cross-reactivity in sera samples significantly correlated with frequency of H1<sup>+</sup>
H5<sup>+</sup>
cross-reactive B cells. Interestingly, only 33% of the cross-reactive sera neutralized both H1N1 and H5N1 pseudoviruses. Cross-reactive and neutralizing antibodies were more prevalent in individuals >50 years of age. Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies. Further, a universal vaccine could be designed to boost pre-existing B-cells expressing stem-directed bNAbs.</p>
</abstract>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Influenza virus</kwd>
<kwd>Viral infection</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2018</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Qatar</li>
<li>États-Unis</li>
</country>
<region><li>Maryland</li>
</region>
</list>
<tree><country name="Qatar"><noRegion><name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M." last="Yassine">Hadi M. Yassine</name>
</noRegion>
<name sortKey="Smatti, Maria K" sort="Smatti, Maria K" uniqKey="Smatti M" first="Maria K." last="Smatti">Maria K. Smatti</name>
</country>
<country name="États-Unis"><region name="Maryland"><name sortKey="Mctamney, Patrick M" sort="Mctamney, Patrick M" uniqKey="Mctamney P" first="Patrick M." last="Mctamney">Patrick M. Mctamney</name>
</region>
<name sortKey="Boyington, Jeffery C" sort="Boyington, Jeffery C" uniqKey="Boyington J" first="Jeffery C." last="Boyington">Jeffery C. Boyington</name>
<name sortKey="Crank, Michelle C" sort="Crank, Michelle C" uniqKey="Crank M" first="Michelle C." last="Crank">Michelle C. Crank</name>
<name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name>
<name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E." last="Ledgerwood">Julie E. Ledgerwood</name>
<name sortKey="Ruckwardt, Tracy J" sort="Ruckwardt, Tracy J" uniqKey="Ruckwardt T" first="Tracy J." last="Ruckwardt">Tracy J. Ruckwardt</name>
</country>
</tree>
</affiliations>
</record>
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