Analysis of the conserved protective epitopes of hemagglutinin on influenza A viruses

The conserved protective epitopes of hemagglutinin (HA) are essential to the design of a universal influenza vaccine and new targeted therapeutic agents. Over the last 15 years, numerous broadly neutralizing antibodies (bnAbs) targeting the HA of influenza A viruses have been isolated from B lymphocytes of human donors and mouse models, and their binding epitopes identified. This work has brought new perspectives for identifying conserved protective epitopes of HA. In this review, we succinctly analyzed and summarized the antigenic epitopes and functions of more than 70 kinds of bnAb. The highly conserved protective epitopes are concentrated on five regions of HA: the hydrophobic groove, the receptor-binding site, the occluded epitope region of the HA monomers interface, the fusion peptide region, and the vestigial esterase subdomain. Our analysis clarifies the distribution of the conserved protective epitope regions on HA and provides distinct targets for the design of novel vaccines and therapeutics to combat influenza A virus infection.