A novel universal influenza vaccine targeting epitopes of limited variability
The antigenic evolution of influenza is conventionally assumed to occur by ‘antigenic drift’ where new strains arise through the incremental addition of mutations in surface glycoproteins. However, the antigenic drift model can only explain the epidemiology and limited genetic diversity observed among influenza virus populations by imposing constraints on the mode and tempo of mutation. We have shown that an alternative model known as ‘antigenic thrift’ successfully models the epidemiology and genetic diversity of influenza by assuming that the antigenic evolution of the virus population is primarily driven by natural immune responses against epitopes of limited variability.   We have identified epitopes of limited variability in H1, H3 and influenza B. Each epitope has between 3 and 4 different conformations. These epitope conformations are all in the head domain of the HAs of various subtypes, making them naturally highly immunogenic. The epitope are also limited in variability, often due to their position adjacent to the receptor binding site, cycling through their limited repertoire of conformations as host population immunity changes.    By vaccinating against these epitope conformations for each subtype, we can induce immunity against all past and present H1, H3 and influenza B. This approach will remove the need to vaccinate each year and have much higher levels of efficacy. The vaccine can also be made using the established methods of inactivated or attenuated influenza vaccine production. This maintains a price threshold of 5 USD per dose, making the vaccine attractive to pharmaceutical companies, and by reducing the number of doses required to confer immunity and while maintaining production cost, the vaccine is attractive to healthcare providers.