DOI: 10.1073/pnas.2316964120 ISSN: 0027-8424

Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin

Joel Finney, Annie Park Moseman, Susan Kong, Akiko Watanabe, Shengli Song, Richard M. Walsh, Masayuki Kuraoka, Ryutaro Kotaki, E. Ashley Moseman, Kevin R. McCarthy, Dongmei Liao, Xiaoe Liang, Xiaoyan Nie, Olivia Lavidor, Richard Abbott, Stephen C. Harrison, Garnett Kelsoe
  • Multidisciplinary

Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against disease by diverse virus subtypes. Only one reported HA Ab, isolated from a combinatorial display library, protects against both IAV and IBV. Thus, there has been so far no information on the likelihood of finding naturally occurring human Abs that bind HAs of diverse IAV subtypes and IBV lineages. We have now recovered from several unrelated human donors five clonal Abs that bind a conserved epitope preferentially exposed in the postfusion conformation of IAV and IVB HA2. These Abs lack neutralizing activity in vitro but in mice provide strong, IgG subtype–dependent protection against lethal IAV and IBV infections. Strategies to elicit similar Abs routinely might contribute to more effective influenza vaccines.

More from our Archive