Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines
Identifieur interne : 002E53 ( Main/Exploration ); précédent : 002E52; suivant : 002E54Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines
Auteurs : Sinthujan Jegaskanda [États-Unis, Australie] ; Sarah F. Andrews ; Adam K. Wheatley [Australie] ; Jonathan W. Yewdell [États-Unis] ; Adrian B. Mcdermott ; Kanta Subbarao [États-Unis]Source :
- JCI Insight [ 2379-3708 ] ; ????.
Abstract
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.
Url:
DOI: 10.1172/jci.insight.129035
PubMed: 31723058
PubMed Central: 6948858
Affiliations:
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Wheatley</name><affiliation wicri:level="1"><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><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></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. 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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 wicri:level="2"><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">JCI Insight</title><idno type="eISSN">2379-3708</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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><affiliations><list><country><li>Australie</li><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Andrews, Sarah F" sort="Andrews, Sarah F" uniqKey="Andrews S" first="Sarah F." last="Andrews">Sarah F. Andrews</name><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B." last="Mcdermott">Adrian B. Mcdermott</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name></region><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Yewdell, Jonathan W" sort="Yewdell, Jonathan W" uniqKey="Yewdell J" first="Jonathan W." last="Yewdell">Jonathan W. Yewdell</name></country><country name="Australie"><noRegion><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name></noRegion><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K." last="Wheatley">Adam K. Wheatley</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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