Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses

• DOI: 10.1016/j.immuni.2024.03.022
• Publication Date: 2024-04-25T14:40:08Z
• Authors: Rashmi Ray; Faez Amokrane Nai...; Daniel P. Maurer; Jiachen Huang; Berk A. Alpay; Larance Ronsard; Zhenfei Xie; Julianna Han; Monica Fernandez-...; Quynh Anh Phan; Rebecca L. Ursin; Mya Vu; Kathrin H. Kirsch; Thavaleak Prum; Victoria C. Rosado; Thalia Bracamonte...; Vintus Okonkwo; Julia Bals; Caitlin McCarthy; Usha Nair; Masaru Kanekiyo; Andrew B. Ward; Aaron G. Schmidt; Facundo D. Batista; Daniel Lingwood
• Keywords: Antibody Repertoire; Group A

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or 2 viral diversity. In rarer cases, intergroup protective bnAbs can generated by human antibody paratopes that accommodate conserved glycan differences between and stems. We applied germline-engaging nanoparticle immunogens elicit a class cross-group from physiological precursor frequency within humanized mouse model. Cross-group protection depended on presence bnAb precursors B cell repertoire, vaccine-expanded enriched for an N55T substitution in CDRH2 loop, hallmark class. Structurally, this single mutation introduced flexible fulcrum glycosylation could alone enable protection. Thus, broad IAV immunity expanded germline repertoire via minimal antigenic input exceptionally simple development pathway.