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

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 ZhangStephanie 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 Kedzierska

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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.

Original languageEnglish
Pages (from-to)966-978
Number of pages13
JournalNature Immunology
Issue number6
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
Aboriginal and Torres Strait Islanders in Australia were respectfully referred to as Australian FN peoples and FN in this paper, as dictated by space and word limit. We thank P. Binks, K. Hosking, T. De Santis, C. Marshall, B. Patel, E. Gargan, J. Webb, M. Dickson, L. H. E. Vintour-Cesar, M. McKinnon, C. Van Wessel and C. Woerle from the Menzies School of Health research and V. Baghbanian, S. Moore and L. Thomas from the Central Australia Aboriginal Congress for participant recruitment and blood processing. This work was supported by the National Health and Medical Research Council (NHMRC) Leadership Investigator Grant to K.K. (no. 1173871) and A.C.C. (no. 1194678), Research Grants Council of the Hong Kong Special Administrative Region (no. T11-712/19-N) to K.K., a Medical Research Future Fund (MRFF) award no. 2005544 to K.K., S.J.K., A.W.C., A.C.C. and J.D., a MRFF award no. 2016062 to K.K., T.H.O.N., L.C.R., S.J.K., J.D., A.W.C., A.C.C., M.P.D., P.G.T., D.S.K. and J.R., an NHMRC Emerging Leadership Level 1 Investigator Grant to T.H.O.N. (no. 1194036), an NHMRC Emerging Leadership Level 2 Investigator Grant to A.W.C. (no. 2009092) and a 2021 Doherty Agility Fund to T.H.O.N., K.K., K.S., A.W.C. and W.Z. W.Z. is supported by the Melbourne Research Scholarship from the University of Melbourne. S.J.K. is supported by an NHMRC Senior Principal Research Fellowship (no. 1136322). J.R. is supported by an Australian Research Council Laureate Fellowship. J.C.C., A.A.M., M.V.P. and P.G.T. are supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) grant nos. R01AI136514 and U01AI150747, and by the American Lebanese Syrian Associated Charities at St. Jude Children’s Research Hospital. S.G. is supported by an NHMRC Senior Research Fellowship (no. 1159272) and the MRFF. This project has been funded in whole or in part with Federal funds from the NIAID/NIH, Department of Health and Human Services, under contract no. 75N93021C00018 (NIAID Centers of Excellence for Influenza Research and Response, CEIRR). This work was supported by the Australian Government Commonwealth Contract-Services (no. E21-24684) to facilitate Central Australia involvement. We thank the Melbourne Cytometry Platform (Peter Doherty Institute and Melbourne Brain Centre nodes) for provision of flow cytometry services. We thank BEI Resources, NIAID and NIH for providing the peptide array, SARS-related coronavirus 2 spike glycoprotein (NR-52402). This research included samples and data from the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases (SETREP-ID). We thank all SETREP-ID investigators and sites and all participants involved. We thank B. Scher for setting up the ethics and governance for the SETREP-ID platform and the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE) for ongoing funding of SETREP-ID. We thank A. Rhodes, J. Chang, A. Dantanarayana and R. Cao who contributed to the SETREP-ID biobank. SETREP-ID is supported by funding from the NHMRC Centre of Research Excellence, APPRISE (ID 1116530), the Snow Medical Foundation, the Jack Ma Foundation and the A2 Milk Company. This research was conducted using samples and data from the Victorian Critical Vaccinees Collection (VC2). We acknowledge the VC2 investigators and sites and the support of the Victorian Government, and thank all the participants involved.

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© 2023, The Author(s).


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