Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

Luca Hensen, Thi H.O. Nguyen, Louise C. Rowntree, Timon Damelang, Marios Koutsakos, Malet Aban, Aeron Hurt, Kim L. Harland, Maria Auladell, Carolien E. van de Sandt, Anngie Everitt, Cath Blacker, Damian A. Oyong, Jessica R. Loughland, Jessica R. Webb, Bruce D. Wines, P. Mark Hogarth, Katie L. Flanagan, Magdalena Plebanski, Adam WheatleyAmy W. Chung, Stephen J. Kent, Adrian Miller, E. Bridie Clemens, Peter C. Doherty, Jane Nelson, Jane Davies, Steven Y.C. Tong, Katherine Kedzierska

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4 Citations (Scopus)


Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the Looking into InFluenza T cell immunity - Vaccination cohort study and collected blood to define baseline, early (day 7), and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells, and antibody profiles and investigated host factors that could contribute to vaccine responses. We found activation profiles of circulating T follicular helper type-1 cells at the early stage correlated strongly with the total change in antibody titers induced by vaccination. Formation of influenza-specific hemagglutinin-binding memory B cells was significantly higher in seroconverters compared with nonseroconverters. In-depth antibody characterization revealed a reduction in immunoglobulin G3 before and after vaccination in the Indigenous Australian population, potentially linked to the increased frequency of the G3m21* allotype. Overall, our data provide evidence that Indigenous populations elicit robust, broad, and prototypical immune responses following immunization with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and their subsequent complications.

Original languageEnglish
Article numbere2109388118
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
Publication statusPublished - 12 Oct 2021


  • Antibodies
  • B cells
  • Follicular T helper cells
  • Indigenous people
  • Influenza

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