Oral Presentation Lorne Infection and Immunity 2023

Robust and prototypical immune responses towards COVID-19 BNT162b2 vaccine in First Nations Australian people are impacted by co-morbidities (#19)

Katherine Kedzierska 1 , Wuji Zhang 1 , Lukasz Kedzierski 1 , Brendon Chua 1 , Mark Mayo 2 , Claire Lonzi 2 , Vanessa Rigas 2 , Bianca Middleton 2 , Hayley McQuilten 1 , Louise Rowntree 1 , Lilith Allen 1 , Ruth Purcell 1 , Hyon Xhi Tan 1 , Jan Petersen 3 , Priyanka Chaurasia 3 , Francesca Mordant 1 , Kanta Subbarao 1 , Florian Krammer 4 , Allen Cheng 5 , Adam Wheatley 1 , Stephen Kent 1 , Jamie Rossjohn 5 , Amy Chung 1 , John Boffa 6 , Adrian Miller 7 , Sarah Lynar 2 , Jane Nelson 2 , Oanh Nguyen 1 , Jane Davies 2
  1. Department of Microbiology & Immunology, University of Melbourne at Doherty Institute, Parkville, VIC, Australia
  2. Menzies School of Health Research, Darwin, TN, Australia
  3. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Vic, Australia
  4. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA
  5. Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia
  6. Central Australian Aboriginal Congress, Alice Springs, ACT, Australia
  7. Indigenous Engagement, CQUniversity, Townville, QLD, Australia

Higher morbidity and mortality rates from pandemic COVID-19 are disproportionately observed in high-risk groups, including Indigenous people globally. We evaluated immune responses in Australian First Nations people and non-Indigenous individuals after COVID-19 BNT162b2 vaccination, and in First Nations people hospitalized with COVID-19. Our study provides evidence that First Nations people elicit effective immune responses following BNT162b2 vaccination: neutralizing antibodies, anti-RBD-antibodies, SARS-CoV-2 Spike-specific B cells, CD4+ and CD8+ T cells measured by activation-induced marker (AIM) assay, IFN‑γ/TNF production and peptide-HLA tetramer staining directly ex vivo. In First Nations participants, RBD IgG antibody titres positively correlated with the body mass index, while negatively correlated with age. Importantly, however, reduced SARS-CoV-2 antibody axis (RBD-antibodies, spike-specific B cells, T follicular helper (Tfh) cells) was found in vaccinated First Nations participants with chronic conditions (diabetes, renal disease). This was strongly associated with altered IgG glycosylation and increased IL-18 levels. First Nations people hospitalized with COVID-19 elicited broad immunity, including RBD/nucleoprotein-antibodies, antibody-secreting cells, Tfh cells, tetramer-specific CD4+/CD8+ T cells with prominent TCR motifs and peptide-stimulated AIM+ T cell frequencies. Our study provides key insights into immune responses following SARS-CoV-2 infection and vaccination in Indigenous people, links for the first-time antibody glycosylation levels to reduced antibody titres post COVID vaccination and emphasizes the importance of vaccine-induced T cells in individuals with co-morbidities.