Immunodominant antibodies against hemagglutinin in ferrets following infection with 2018 to 2019 influenza vaccine strains

Global influenza surveillance depends on antigenic characterization of viral isolates through hemagglutination inhibition and microneutralization assays using sera from panels of ferrets, each infected with a single vaccine virus. However, recent studies have revealed limitations in ferret-based antigenic analyses. Therefore, a deeper understanding of ferret antibody responses following viral infection is essential for better evaluation and interpretation of antigenicity data derived from ferret sera. This study utilized a biolayer interferometry (BLI)-based binding assay and panels of recombinant hemagglutinin (rHA1), each carrying multiple substitutions within one of the antigenic sites of H1 or H3 HA, to analyze the immunodominant antibodies against HA in ferret sera following infection with the 2018-2019 Northern Hemisphere influenza vaccine virus A/Michigan/45/2015(H1N1)pdm09 (MI/45) or A/Singapore/INFIMH-16-0019/2016(H3N2) (SING/16). The results demonstrate dominant antibody responses against HA in ferrets and provide valuable insights into interpreting ferret-derived antigenicity data and improving influenza vaccine virus selection.