부산대학교 도서관

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine. Author summary: Growing influenza virus in chicken eggs remains a widely used method for producing seasonal influenza vaccines. However, it is common for influenza virus to acquire mutations on the hemagglutinin (HA) protein to facilitate their growth in eggs. These egg-adaptive mutations may change the antigenic property of HA and thus decrease the vaccine effectiveness, as exemplified by mutation L194P. In this study, we demonstrate that two natural variants Thr160 and Asn190 in recently circulating human H3N2 strains can prevent the emergence of L194P. Consistently, we also show that the preference of egg-adaptive mutation varies from strains to strains, with various previously uncharacterized egg-adaptive mutations in recent human H3N2 clades. These observations indicate that the preference of egg-adaptive mutation changes as human influenza virus evolves over time. Overall, our findings provide important insights into the mechanism of egg-adaptation of influenza virus and have important implications for the development of more effective influenza vaccines. [ABSTRACT FROM AUTHOR]