Hensen L

Nguyen THO

Rowntree LC

Damelang T

Koutsakos M

Aban M

Hurt A

Harland KL

Auladell M

van de Sandt CE

Everitt A

Blacker C

Oyong DA

Loughland, JR

Webb JR

Wines BD

Hogarth PM

Flanagan KL

Plebanski M

Wheatley A

Chung AW

Kent SJ

Miller A

Clemens EB

Doherty PC

Nelson J

Davies J

Tong SYC

Kedzierska K

2021-10-12

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.

Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3000, Australia.

World Health Organization Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.

Menzies School of Health Research, Charles Darwin University, Darwin, NT 0810, Australia.

Center for Global Infectious Disease Research (CGIDR), Seattle Children's Research Institute, Seattle, WA 98109.

Immunology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.

Immune Therapies Laboratory, Burnet Institute, Melbourne, VIC 3084, Australia.

Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3010, Australia.

Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.

Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Launceston, TAS 7250, Australia.

School of Health Sciences and School of Medicine, University of Tasmania, Launceston, TAS 7248, Australia.

Department of Immunology and Pathology, Monash University, Melbourne, VIC 3800, Australia.

School of Health and Biomedical Science, Royal Melbourne Institute of Technology, Melbourne, VIC 3000, Australia.

Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3010, Australia.

Infectious Diseases Department, Melbourne Sexual Health Centre, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC 3053, Australia.

Indigenous Engagement, Central Queensland University, Townsville, QLD 4810, Australia.

Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3000, Australia; pcd@unimelb.edu.au kkedz@unimelb.edu.au.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.

Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT 0810, Australia.

Victorian Infectious Diseases Service, The Royal Melbourne Hospital and The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3000, Australia.

Copyright © 2021 the Author(s). Published by PNAS.

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2109388118. doi: 10.1073/pnas.2109388118.

0000-0001-8467-8537

0000-0002-9294-7693

0000-0002-0649-5089

0000-0001-9994-9723

0000-0002-4155-7433

0000-0002-1575-1953

0000-0002-5593-9387

0000-0003-0020-9704

0000-0002-8539-4891

0000-0002-1368-8356

0000-0001-6141-335X

https://pubmed.ncbi.nlm.nih.gov/34607957/?otool=iaurydwlib

https://hdl.handle.net/10137/11929

118

Antibodies, Viral / blood*

Australia

B-Lymphocytes / immunology

Humans

Immunoglobulin G / blood

Immunologic Memory / immunology

Indigenous Peoples / statistics & numerical data*

Influenza Vaccines / immunology*

Influenza, Human / immunology

Influenza, Human / prevention & control*

Influenza, Human / virology

Influenza, Human / virology

Lymphocyte Activation / immunology*

Mass Vaccination

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

Journal Article

Publication