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Publication Abstract from PubMed

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

Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.,Ray R, Nait Mohamed FA, Maurer DP, Huang J, Alpay BA, Ronsard L, Xie Z, Han J, Fernandez-Quintero M, Phan QA, Ursin RL, Vu M, Kirsch KH, Prum T, Rosado VC, Bracamonte-Moreno T, Okonkwo V, Bals J, McCarthy C, Nair U, Kanekiyo M, Ward AB, Schmidt AG, Batista FD, Lingwood D Immunity. 2024 Apr 18:S1074-7613(24)00143-2. doi: 10.1016/j.immuni.2024.03.022. PMID:38670113^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.