Stability of hemagglutinin: toward a universal influenza vaccine

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations. Due to the drawbacks of current vaccines with low vaccine effectiveness, there is an urgent need for universal vaccine development against influenza viruses. Antigenic variation is an essential strategy of the virus to change epitopes, receptor binding or fusion with the host membrane and is associated with changes in amino acid sequences of viral proteins. This antigenic drift is largely focused on viral major protein hemagglutinin (HA) that is the major antigen target. It has been recognized that primary mutations affecting HA functions require co-mutations that modulate the stability of HA for viral infection, which is not yet clearly understood. This review summarizes recent advances in the field of influenza vaccines with regard to HA protein stability.