Structural Insights for Anti-Influenza Vaccine Design

Influenza A virus are a persistent and significant threat to human health, and current vaccines do not provide sufficient protection due to antigenic drift, which allows influenza viruses to easily escape immune surveillance and antiviral drug activity. Influenza hemagglutinin (HA) is a glycoprotein needed for the entry of enveloped influenza viruses into host cells and is a potential target for anti-influenza humoral immune responses. In recent years, a number of broadly neutralizing antibodies (bnAbs) have been isolated, and their relative structural information obtained from the crystallization of influenza antigens in complex with bnAbs has provided some new insights into future influenza vaccine research. Here, we review the current knowledge of the HA-targeted bnAbs and the structure-based mechanisms contributing to neutralization. We also discuss the potential for this structure-based approach to overcome the challenge of obtaining a highly desired "universal" influenza vaccine, especially on small proteins and peptides.