Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera
Identifieur interne : 000008 ( 1968/Analysis ); précédent : 000007; suivant : 000009Use 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
Affiliations:
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PMC:5988737Le document en format XML
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Smatti</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">Qatar</country><wicri:regionArea>Doha</wicri:regionArea></affiliation></author><author><name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E." last="Ledgerwood">Julie E. 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Graham</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Noda, T" uniqKey="Noda T">T Noda</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nabel, Gj" uniqKey="Nabel G">GJ Nabel</name></author><author><name sortKey="Fauci, As" uniqKey="Fauci A">AS Fauci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Throsby, M" uniqKey="Throsby M">M Throsby</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sui, J" uniqKey="Sui J">J Sui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dreyfus, C" uniqKey="Dreyfus C">C Dreyfus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corti, D" uniqKey="Corti D">D Corti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekiert, Dc" uniqKey="Ekiert D">DC Ekiert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wrammert, J" uniqKey="Wrammert J">J Wrammert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corti, D" uniqKey="Corti D">D Corti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kashyap, Ak" uniqKey="Kashyap A">AK Kashyap</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lingwood, D" uniqKey="Lingwood D">D Lingwood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yassine, Hm" uniqKey="Yassine H">HM Yassine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Margine, I" uniqKey="Margine 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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>Pour manipuler ce document sous Unix (Dilib)
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