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

Abstract

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.

Broad spectrum SARS‐CoV‐2‐specific immunity in hospitalized First Nations peoples recovering from COVID‐19

“…Our recent study showed robust immune responses towards COVID‐19 vaccination in Australian First Nations peoples, although reduced antibody responses were found in individuals with diabetes and renal diseases 8 . Similarly, previously we highlighted that Australian First Nations peoples can mount robust immune responses towards seasonal influenza vaccination 9 . Yet, Australian First Nations peoples are still disproportionately affected by severe influenza disease, as evidenced by the 2009 influenza pandemic and seasonal influenza epidemics 10,11 .…”

“…Samples were taken at Visit 1 (V1, enrolment, n = 13) and Visit 2 (V2, hospital discharge, n = 10). Heparinized peripheral blood and serum were collected for isolating peripheral blood monocular cells (PBMCs), plasma, sera and granulocytes 9 . Bloods were shipped overnight from the Menzies School of Health Research to the University of Melbourne for immediate blood processing and whole blood analyses.…”

“…8 Similarly, previously we highlighted that Australian First Nations peoples can mount robust immune responses towards seasonal influenza vaccination. 9 Yet, Australian First Nations peoples are still disproportionately affected by severe influenza disease, as evidenced by the 2009 influenza pandemic and seasonal influenza epidemics. 10,11 Therefore, scant data exist on whether immunological factors contribute to disease susceptibility and severity towards SARS-CoV-2 infection or other respiratory viral infections in Indigenous peoples, but are urgently needed to inform rational strategical planning and to better protect Indigenous populations globally.…”

Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques

“…To simultaneously define multidimensional antibody features elicited after WPV and SV immunization, a 28-parameter multiplex bead array was performed [ 26 , 27 ]. Trimeric HA and monomeric NA (from A/H1N1, A/H3N2 and B/Phuket) as well as HA Stem (from A/H1N1) and NP antigens were used for detecting a range of epitope-specific antibody isotypes (IgA and IgG) and Fcγ receptor binding (FcγR2a and FcγR3a) ( Fig 1A[ii] and S2 Table ).…”

“…Antigens were covalently coupled to magnetic carboxylated beads using a two-step carbodiimide reaction as previously described [ 26 , 27 ]. Briefly, antigen-coupled beads (500–750 beads per bead region) were pooled and combined with diluted plasma (IgG; 1:600, IgA; 1:400, FcγR2 and FcγR3; 1:200) overnight before washing and staining with detectors (PE-conjugated anti-human IgG and IgA antibodies or soluble dimeric FcγR followed by streptavidin PE conjugate) ( S2 Table ).…”