Background
Repeated administration of influenza vaccines appears to incrementally attenuate immunogenicity and effectiveness, especially when successive vaccines are antigenically similar. Although these effects appear to be worse for A(H3N2), they are also observed for A(H1N1)pdm09, which has shown increasing antigenic diversity in recent years.
Methods
A cohort of Australian health care workers (HCWs) was followed for post-vaccination antibody responses across two years during which influenza did not circulate (2020-2021). Vaccine administered in 2020 contained an A/Brisbane/02/2018-like H1N1 antigen, while in 2021 an antigenically distinct A/Victoria/2570/2019-like antigen was included. Pre-vaccination, 14 days and 7 months post-vaccination sera were assessed in haemagglutination inhibition (HI) assay against influenza A(H1N1)pdm09 vaccine viruses from the corresponding years to assess pre/post vaccination antibody titres. Differences in titre were compared by prior vaccination history.
Results
A total of 1384 HCWs contributed sera in the two years. Among them, 96 were previously unvaccinated (vaccinated in 0/5 prior years) and 778 were frequently vaccinated (≥5/5 prior years). While frequent vaccination attenuated titres and titre rises in both years, the effect was substantially diminished in 2021. Notably, only 16% of frequently vaccinated versus 80% of previously unvaccinated HCWs seroconverted in 2020 versus 80% and 86%, respectively in 2021.
The 2021 vaccine strain differed from all prior H1N1pdm09 vaccines at HA positions N129D, K130N and N156K, which are within prominent antigenic sites. Additionally, only the 2021 vaccine strain had 185I, which was present in seasonal H1N1s. We are currently investigating whether these substitutions facilitated a stronger or more specific immune response through mechanisms such as escape from memory dominance or recall of memory against prior seasonal strains. Sera are being titrated against viruses from the alternate year, and against reverse genetics viruses bearing single substitutions. PBMC’s are being assessed to compare the frequency and phenotype of H1 HA reactive B cells induced.
Conclusions
The H1N1 vaccine antigen used in 2021 induced substantially greater antibody responses than the 2020 antigen, particularly among frequently vaccinated HCW. Investigations are underway to understand how antigenic changes in the 2021 antigen may have enhanced immunogenicity.