Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
Publication/Presentation Date
5-14-2024
Abstract
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.
Volume
57
Issue
5
First Page
1141
Last Page
1159
ISSN
1097-4180
Published In/Presented At
Ray, R., Nait Mohamed, F. A., Maurer, D. P., Huang, J., Alpay, B. A., Ronsard, L., Xie, Z., Han, J., Fernandez-Quintero, M., Phan, Q. A., Ursin, R. L., Vu, M., Kirsch, K. H., Prum, T., Rosado, V. C., Bracamonte-Moreno, T., Okonkwo, V., Bals, J., McCarthy, C., Nair, U., … Lingwood, D. (2024). Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses. Immunity, 57(5), 1141–1159.e11. https://doi.org/10.1016/j.immuni.2024.03.022
Disciplines
Medicine and Health Sciences
PubMedID
38670113
Department(s)
Medical Education
Document Type
Article