A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

TLDR

Current flu vaccines cover only a limited range of seasonal strains, but the discovery of V(H)1‑69 antibodies that broadly neutralize most influenza A group 1 viruses marked a breakthrough. The study reports the isolation and characterization of CR8020, a human monoclonal antibody with broad neutralizing activity against group 2 influenza A viruses. CR8020 was isolated from a human donor and characterized by binding and neutralization assays against H3N2 and H7N7 strains. The crystal structure of CR8020 Fab bound to H3 HA reveals a highly conserved stalk epitope distinct from V(H.

Abstract

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.