Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4⁺ and CD8⁺ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.Wuji Zhang, Lukasz Kedzierski, Brendon Y. Chua, Mark Mayo, Claire Lonzi, Vanessa Rigas, Bianca F. Middleton, Hayley A. McQuilten, Louise C. Rowntree, Lilith F. Allen, Ruth A. Purcell, Hyon-Xhi Tan, Jan Petersen, Priyanka Chaurasia, Francesca Mordant, Mikhail V. Pogorelyy, Anastasia A. Minervina, Jeremy Chase Crawford, Griffith B. Perkins, Eva Zhang, Stephanie Gras, E. Bridie Clemens, Jennifer A. Juno, Jennifer Audsley, David S. Khoury, Natasha E. Holmes, Irani Thevarajan, Kanta Subbarao, Florian Krammer, Allen C. Cheng, Miles P. Davenport, Branka Grubor-Bauk, P. Toby Coates, Britt Christensen, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Amy W. Chung, John Boffa, Adrian Miller, Sarah Lynar, Jane Nelson, Thi H. O. Nguyen, Jane Davies, Katherine Kedziersk