Hemagglutinin destabilization in H3N2 vaccine reference viruses skews antigenicity and prevents airborne transmission in ferrets

During influenza virus entry, the hemagglutinin (HA) protein binds receptors and causes membrane fusion after endosomal acid activation. To improve vaccine efficiency and pandemic risk assessment for currently-dominant H3N2 influenza viruses, we investigated HA stability of 6 vaccine reference viruses and 42 circulating viruses. Recent vaccine reference viruses had destabilized HA proteins due to egg-adaptive mutation HA1-L194P. Virus growth in cell culture was independent of HA stability. In ferrets, the vaccine reference viruses and circulating viruses required a relatively stable HA (activation and inactivation pH  SIGN UP FOR THE SCIENCE ADVANCES eTOC Get the latest table of contents from Science Advances delivered right to you! Sign up sessionStorage.alertlast = "Science Advances eTOC"; sessionStorage.alertlastdoi = "10.1126/sciadv.adf5182";