{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:59:36Z","timestamp":1788965976828,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00052"],"award-info":[{"award-number":["75N93019C00052"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00051"],"award-info":[{"award-number":["75N93019C00051"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["K01OD026569"],"award-info":[{"award-number":["K01OD026569"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM109435"],"award-info":[{"award-number":["GM109435"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Computationally optimized broadly reactive Ag (COBRA) hemagglutinin (HA) immunogens have previously been generated for several influenza subtypes to improve vaccine-elicited Ab breadth. As nearly all individuals have pre-existing immunity to influenza viruses, influenza-specific memory B cells will likely be recalled upon COBRA HA vaccination. We determined the epitope specificity and repertoire characteristics of pre-existing human B cells to H1 COBRA HA Ags. Cross-reactivity between wild-type HA and H1 COBRA HA proteins P1, X6, and Y2 were observed for isolated mAbs. The mAbs bound five distinct epitopes on the pandemic A\/California\/04\/2009 HA head and stem domains, and most mAbs had hemagglutination inhibition and neutralizing activity against 2009 pandemic H1 strains. Two head-directed mAbs, CA09-26 and CA09-45, had hemagglutination inhibition and neutralizing activity against a prepandemic H1 strain. One mAb, P1-05, targeted the stem region of H1 HA, but did not compete with a known stem-targeting H1 mAb. We determined that mAb P1-05 recognizes a recently discovered HA epitope, the anchor epitope, and we identified similar mAbs using B cell repertoire sequencing. In addition, the trimerization domain distance from HA was critical to recognition of this epitope by mAb P1-05, suggesting the importance of protein design for vaccine formulations. Overall, these data indicate that seasonally vaccinated individuals possess a population of functional H1 COBRA HA\u2013reactive B cells that target head, central stalk, and anchor epitopes, and they demonstrate the importance of structure-based assessment of subunit protein vaccine candidates to ensure accessibility of optimal protein epitopes.<\/jats:p>","DOI":"10.4049\/jimmunol.2101171","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T15:13:32Z","timestamp":1657725212000},"page":"5-15","source":"Crossref","is-referenced-by-count":16,"title":["The Pre-Existing Human Antibody Repertoire to Computationally Optimized Influenza H1 Hemagglutinin Vaccines"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-6651","authenticated-orcid":false,"given":"Kaito","family":"Nagashima","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia , Athens, GA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-146X","authenticated-orcid":false,"given":"John V","family":"Dzimianski","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California Santa Cruz , Santa Cruz, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3402-2609","authenticated-orcid":false,"given":"Julianna","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Abbadi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia , Athens, GA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D","family":"Gingerich","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-2431","authenticated-orcid":false,"given":"Fredejah","family":"Royer","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8624-0483","authenticated-orcid":false,"given":"Sara","family":"O\u2019Rourke","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California Santa Cruz , Santa Cruz, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-2235","authenticated-orcid":false,"given":"Giuseppe A","family":"Sautto","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia , Athens, GA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-5673","authenticated-orcid":false,"given":"Rebecca M","family":"DuBois","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering, University of California Santa Cruz , Santa Cruz, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4709-2478","authenticated-orcid":false,"given":"Jarrod J","family":"Mousa","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia , Athens, GA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia , Athens, GA"},{"name":"Department of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia , Athens, 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