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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines</title>
<author><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrews, Sarah F" sort="Andrews, Sarah F" uniqKey="Andrews S" first="Sarah F." last="Andrews">Sarah F. Andrews</name>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K." last="Wheatley">Adam K. Wheatley</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yewdell, Jonathan W" sort="Yewdell, Jonathan W" uniqKey="Yewdell J" first="Jonathan W." last="Yewdell">Jonathan W. Yewdell</name>
<affiliation><nlm:aff id="A4">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B." last="Mcdermott">Adrian B. Mcdermott</name>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31723058</idno>
<idno type="pmc">6948858</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948858</idno>
<idno type="RBID">PMC:6948858</idno>
<idno type="doi">10.1172/jci.insight.129035</idno>
<date when="????">????</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines</title>
<author><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrews, Sarah F" sort="Andrews, Sarah F" uniqKey="Andrews S" first="Sarah F." last="Andrews">Sarah F. Andrews</name>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K." last="Wheatley">Adam K. Wheatley</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yewdell, Jonathan W" sort="Yewdell, Jonathan W" uniqKey="Yewdell J" first="Jonathan W." last="Yewdell">Jonathan W. Yewdell</name>
<affiliation><nlm:aff id="A4">Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B." last="Mcdermott">Adrian B. Mcdermott</name>
<affiliation><nlm:aff wicri:cut=" and" id="A3">Vaccine Research Center</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">JCI Insight</title>
<idno type="eISSN">2379-3708</idno>
<imprint><date when="????">????</date>
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<front><div type="abstract" xml:lang="en"><p>Broadly neutralizing Abs targeting the HA stem can provide broad protection against different influenza subtypes, raising the question of how best to elicit such Abs. We have previously demonstrated that vaccination with pandemic live-attenuated influenza vaccine (pLAIV) establishes immune memory for HA head-specific Abs. Here, we determine the extent to which matched versus mismatched LAIV-inactivated subunit vaccine (IIV) prime-boost vaccination elicits stem-specific memory B cells and Abs. We vaccinated African green monkeys with H5N1 pLAIV-pIIV or H5N1 pLAIV followed by seasonal IIV (sIIV) or with H5N1 pLAIV alone and measured Abs and HA-specific B cell responses. While we observed an increase in stem-specific memory B cells, head-specific memory B cell responses were substantially higher than stem-specific responses and were dominant even following boost with mismatched IIV. Neutralizing Abs against heterologous influenza viruses were undetectable. Head-specific B cells from draining lymph nodes exhibited germinal center markers, while stem-specific B cells found in the spleen and peripheral blood did not. Thus, although mismatched prime-boost generated a pool of stem-specific memory B cells, head-specific B cells and serum Abs substantially dominated the immune response. These findings have implications for including full-length native HA in prime-boost strategies intended to induce stem-specific Abs for universal influenza vaccination.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">JCI Insight</journal-id>
<journal-id journal-id-type="iso-abbrev">JCI Insight</journal-id>
<journal-id journal-id-type="publisher-id">JCI Insight</journal-id>
<journal-title-group><journal-title>JCI Insight</journal-title>
</journal-title-group>
<issn pub-type="epub">2379-3708</issn>
<publisher><publisher-name>American Society for Clinical Investigation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31723058</article-id>
<article-id pub-id-type="pmc">6948858</article-id>
<article-id pub-id-type="publisher-id">129035</article-id>
<article-id pub-id-type="doi">10.1172/jci.insight.129035</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Jegaskanda</surname>
<given-names>Sinthujan</given-names>
</name>
<email>jegaskanda8@gmail.com</email>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-2583-1949</contrib-id>
<name><surname>Andrews</surname>
<given-names>Sarah F.</given-names>
</name>
<email>sarah.andrews2@nih.gov</email>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-5593-9387</contrib-id>
<name><surname>Wheatley</surname>
<given-names>Adam K.</given-names>
</name>
<email>a.wheatley@unimelb.edu.au</email>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yewdell</surname>
<given-names>Jonathan W.</given-names>
</name>
<email>jyewdell@mail.nih.gov</email>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McDermott</surname>
<given-names>Adrian B.</given-names>
</name>
<email>adrian.mcdermott@nih.gov</email>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Subbarao</surname>
<given-names>Kanta</given-names>
</name>
<email>kanta.subbarao@influenzacentre.org</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</aff>
<aff id="A2"><label>2</label>
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.</aff>
<aff id="A3"><label>3</label>
Vaccine Research Center and</aff>
<aff id="A4"><label>4</label>
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.</aff>
<author-notes><corresp>Address correspondence to: Kanta Subbarao, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland 20892, USA. Phone: 301.451.3839; Email: <email>ksubbarao@niaid.nih.gov</email>
.</corresp>
<fn fn-type="COI-statement"><p><bold>Conflict of interest:</bold>
The authors have declared that no conflict of interest exists.</p>
</fn>
</author-notes>
<pub-date date-type="pub" publication-format="electronic" iso-8601-date="2019-11-14T09:00:00-0500"><day>14</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date date-type="collection" publication-format="electronic" iso-8601-date="2019-11-14T09:00:00-0500"><day>14</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>14</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>4</volume>
<issue>22</issue>
<elocation-id>e129035</elocation-id>
<history><date date-type="received"><day>17</day>
<month>4</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>9</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 American Society for Clinical Investigation</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>American Society for Clinical Investigation</copyright-holder>
</permissions>
<self-uri xlink:href="https://insight.jci.org/articles/view/129035">This article is available online at https://insight.jci.org/articles/view/129035</self-uri>
<abstract><p>Broadly neutralizing Abs targeting the HA stem can provide broad protection against different influenza subtypes, raising the question of how best to elicit such Abs. We have previously demonstrated that vaccination with pandemic live-attenuated influenza vaccine (pLAIV) establishes immune memory for HA head-specific Abs. Here, we determine the extent to which matched versus mismatched LAIV-inactivated subunit vaccine (IIV) prime-boost vaccination elicits stem-specific memory B cells and Abs. We vaccinated African green monkeys with H5N1 pLAIV-pIIV or H5N1 pLAIV followed by seasonal IIV (sIIV) or with H5N1 pLAIV alone and measured Abs and HA-specific B cell responses. While we observed an increase in stem-specific memory B cells, head-specific memory B cell responses were substantially higher than stem-specific responses and were dominant even following boost with mismatched IIV. Neutralizing Abs against heterologous influenza viruses were undetectable. Head-specific B cells from draining lymph nodes exhibited germinal center markers, while stem-specific B cells found in the spleen and peripheral blood did not. Thus, although mismatched prime-boost generated a pool of stem-specific memory B cells, head-specific B cells and serum Abs substantially dominated the immune response. These findings have implications for including full-length native HA in prime-boost strategies intended to induce stem-specific Abs for universal influenza vaccination.</p>
</abstract>
<abstract abstract-type="toc"><p>Priming and boosting with mismatched influenza vaccines elicited more HA head- than stem-specific memory B cells and did not induce broadly cross-neutralizing antibodies.</p>
</abstract>
<kwd-group kwd-group-type="specialties"><kwd>Infectious disease</kwd>
<kwd>Vaccines</kwd>
</kwd-group>
<kwd-group kwd-group-type="keywords"><kwd>Influenza</kwd>
</kwd-group>
<funding-group><award-group><funding-source>NIAID, NIH</funding-source>
<award-id>N/A</award-id>
</award-group>
<funding-statement>Division of Intramural Research</funding-statement>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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