H5N1 vaccine-elicited memory B cells are genetically constrained by the IGHV locus in the recognition of a neutralizing epitope in the HA stem
Identifieur interne : 000560 ( Main/Exploration ); précédent : 000559; suivant : 000561H5N1 vaccine-elicited memory B cells are genetically constrained by the IGHV locus in the recognition of a neutralizing epitope in the HA stem
Auteurs : Adam K. Wheatley [États-Unis] ; James Rr Whittle [États-Unis] ; Daniel Lingwood [États-Unis] ; Masaru Kanekiyo [États-Unis] ; Hadi M. Yassine [États-Unis] ; Steven S. Ma [États-Unis] ; Sandeep R. Narpala [États-Unis] ; Madhu S. Prabhakaran [États-Unis] ; Rodrigo A. Matus-Nicodemos [États-Unis] ; Robert T. Bailer [États-Unis] ; Gary J. Nabel [États-Unis] ; Barney S. Graham [États-Unis] ; Julie E. Ledgerwood [États-Unis] ; Richard A. Koup [États-Unis] ; Adrian B. Mcdermott [États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2015.
Abstract
Due to significant viral diversity, vaccines that elicit durable and broad protection against influenza have been elusive. Recent research has focused on the potential of highly conserved regions of the viral hemagglutinin (HA) as targets for broadly neutralizing antibody responses. Antibodies that bind the highly conserved stem or stalk of HA can be elicited by vaccination in humans and animal models and neutralize diverse influenza strains. However, the frequency and phenotype of HA stem-specific B cells in vivo remains unclear. Here we characterize HA stem-specific B cell responses following H5N1 vaccination and describe the re-expansion of a pre-existing population of memory B cells specific for stem epitopes. This population utilizes primarily, but not exclusively, IGHV1-69-based immunoglobulins for HA recognition. However within some subjects, allelic polymorphism at the
Url:
DOI: 10.4049/jimmunol.1402835
PubMed: 26078272
PubMed Central: 4491024
Affiliations:
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Wheatley</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Whittle, James Rr" sort="Whittle, James Rr" uniqKey="Whittle J" first="James Rr" last="Whittle">James Rr Whittle</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><affiliation wicri:level="2"><nlm:aff id="A3"> Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kanekiyo, Masaru" sort="Kanekiyo, Masaru" uniqKey="Kanekiyo M" first="Masaru" last="Kanekiyo">Masaru Kanekiyo</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M" last="Yassine">Hadi M. Yassine</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ma, Steven S" sort="Ma, Steven S" uniqKey="Ma S" first="Steven S" last="Ma">Steven S. Ma</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Narpala, Sandeep R" sort="Narpala, Sandeep R" uniqKey="Narpala S" first="Sandeep R" last="Narpala">Sandeep R. Narpala</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Prabhakaran, Madhu S" sort="Prabhakaran, Madhu S" uniqKey="Prabhakaran M" first="Madhu S" last="Prabhakaran">Madhu S. Prabhakaran</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Matus Nicodemos, Rodrigo A" sort="Matus Nicodemos, Rodrigo A" uniqKey="Matus Nicodemos R" first="Rodrigo A" last="Matus-Nicodemos">Rodrigo A. Matus-Nicodemos</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bailer, Robert T" sort="Bailer, Robert T" uniqKey="Bailer R" first="Robert T" last="Bailer">Robert T. Bailer</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name><affiliation wicri:level="2"><nlm:aff id="A2"> Sanofi, Cambridge, Massachusetts, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Sanofi, Cambridge, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E" last="Ledgerwood">Julie E. Ledgerwood</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A" last="Koup">Richard A. Koup</name><affiliation wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><nlm:aff id="A1"> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Due to significant viral diversity, vaccines that elicit durable and broad protection against influenza have been elusive. Recent research has focused on the potential of highly conserved regions of the viral hemagglutinin (HA) as targets for broadly neutralizing antibody responses. Antibodies that bind the highly conserved stem or stalk of HA can be elicited by vaccination in humans and animal models and neutralize diverse influenza strains. However, the frequency and phenotype of HA stem-specific B cells in vivo remains unclear. Here we characterize HA stem-specific B cell responses following H5N1 vaccination and describe the re-expansion of a pre-existing population of memory B cells specific for stem epitopes. This population utilizes primarily, but not exclusively, IGHV1-69-based immunoglobulins for HA recognition. However within some subjects, allelic polymorphism at the <italic>ighv1-69</italic> locus can limit IGHV1-69 immunodominance and may reduce circulating frequencies of stem-reactive B cells in vivo. The accurate definition of allelic selection, recombination requirements and ontogeny of neutralizing antibody responses to influenza will aid rational influenza vaccine design.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Wheatley, Adam K" sort="Wheatley, Adam K" uniqKey="Wheatley A" first="Adam K" last="Wheatley">Adam K. Wheatley</name></region><name sortKey="Bailer, Robert T" sort="Bailer, Robert T" uniqKey="Bailer R" first="Robert T" last="Bailer">Robert T. Bailer</name><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S" last="Graham">Barney S. Graham</name><name sortKey="Kanekiyo, Masaru" sort="Kanekiyo, Masaru" uniqKey="Kanekiyo M" first="Masaru" last="Kanekiyo">Masaru Kanekiyo</name><name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A" last="Koup">Richard A. Koup</name><name sortKey="Ledgerwood, Julie E" sort="Ledgerwood, Julie E" uniqKey="Ledgerwood J" first="Julie E" last="Ledgerwood">Julie E. Ledgerwood</name><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><name sortKey="Ma, Steven S" sort="Ma, Steven S" uniqKey="Ma S" first="Steven S" last="Ma">Steven S. Ma</name><name sortKey="Matus Nicodemos, Rodrigo A" sort="Matus Nicodemos, Rodrigo A" uniqKey="Matus Nicodemos R" first="Rodrigo A" last="Matus-Nicodemos">Rodrigo A. Matus-Nicodemos</name><name sortKey="Mcdermott, Adrian B" sort="Mcdermott, Adrian B" uniqKey="Mcdermott A" first="Adrian B" last="Mcdermott">Adrian B. Mcdermott</name><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J" last="Nabel">Gary J. Nabel</name><name sortKey="Narpala, Sandeep R" sort="Narpala, Sandeep R" uniqKey="Narpala S" first="Sandeep R" last="Narpala">Sandeep R. Narpala</name><name sortKey="Prabhakaran, Madhu S" sort="Prabhakaran, Madhu S" uniqKey="Prabhakaran M" first="Madhu S" last="Prabhakaran">Madhu S. Prabhakaran</name><name sortKey="Whittle, James Rr" sort="Whittle, James Rr" uniqKey="Whittle J" first="James Rr" last="Whittle">James Rr Whittle</name><name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M" last="Yassine">Hadi M. Yassine</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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