The mutational variety of the live-attenuated influenza vaccine proteome

Influenza viruses evolve rapidly, and for this reason the influenza vaccine needs to be updated every year. It is therefore important to identify where new mutations could be tolerated. To assess this, we asked which mutations could be identified in the proteins that had passed quality checks by being correctly folded, transported and assembled into influenza virus particles. We re-analysed mass spectrometry proteomics data obtained from the virus particles of genetically well-defined vaccine strains and identified point mutations within viral proteins. Point mutations were tolerated in virus particles at appreciable frequencies in proteins of both influenza A and B viruses, including HA, NA, M1, NP, NS1, PA and PB2. Structural analyses were used to assess the likely impact of this protein diversity on the molecular biology of the virus. As would be expected, mutations that were tolerated the virus particle generally occurred at sites that would not be expected to perturb protein function. We suggest that using proteomics to identify sites in viral proteins that either can or cannot tolerate mutations could inform influenza vaccine development by highlighting areas that have the potential for antigenic drift.