Immune responses to an inactivated influenza vaccine in Indigenous Australians

Abstract

Abstract Indigenous Australians are highly susceptible to severe influenza disease during seasonal and pandemic infections. Current antibody-based vaccines targeting humoral immunity are the most effective way to combat influenza infections but show reduced efficacy in Indigenous Australians. The underlying mechanisms are still unknown. We recruited 166 Indigenous & non-Indigenous donors to elucidate adaptive immune responses induced by the inactivated quadrivalent influenza vaccine. Participants were bled at baseline, day 7 and day 28 post-vaccination. We analysed hemagglutination inhibition titres against the vaccine and previously circulating strains, analysed IgG1 and IgG3 allotypes, evaluated total IgG glycosylation and performed Luminex assays to dissect antibody responses against viral HA, NA and NP proteins. Additionally, we assessed influenza-specific B cell responses with fluorescent HA probes, antibody-secreting cells and circulating Tfh cells. More than 15,000 datapoints were collected to compare adaptive immune responses between Indigenous and non-Indigenous donors. We found that the majority of immune readouts were comparable between the two groups. However, interestingly, we found significantly lower pre-vaccine titres and lower back-boosting to pre-pandemic H1N1 viruses in Indigenous compared to non-Indigenous donors. This might explain, at least in part, high susceptibility of Indigenous Australians to the 2009 pandemic. Our comprehensive dataset will be used to understand and improve optimal vaccine responses in Indigenous and non-Indigenous populations globally.