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

Luca Hensen ,Stephen J Kent ,Peter C Doherty ,Adam K Wheatley ,Katie L Flanagan ,Magdalena Plebanski ,Marios Koutsakos ,Steven Y C Tong ,Adrian Miller ,Thi H O Nguyen ,Louise C Rowntree ,Damian Oyong ,Jane Nelson ,Cath Blacker ,P Mark Hogarth ,Amy W Chung ,E Bridie Clemens ,Maria Auladell ,Bruce D Wines ,Jane Davies ,Aeron C Hurt ,Malet Aban ,Anngie Everitt ,Timon Damelang ,Carolien E Van De Sandt ,Jessica R Webb ,Jessica R Loughland ,Kim L Harland ,Katherine Kedzierska

doi:10.1073/pnas.2109388118

Abstract

SignificanceIndigenous populations worldwide are highly susceptible to influenza virus infections. Vaccination with inactivated virus is highly recommended to protect Indigenous populations, including Indigenous Australians. There is no study to date that assessed immune responses induced by the inactivated seasonal influenza vaccine in the Indigenous population. Vaccine recommendations are thus based on data generated for non-Indigenous populations and might not be representative for Indigenous people. We found robust antibody responses to influenza vaccination induced in Indigenous Australians, with activation profiles of cTFH1 cells at the acute response strongly correlating with total change of antibody vaccine titers induced by vaccination. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and subsequent complications.

Highlights

We found robust antibody responses to influenza vaccination induced in Indigenous Australians, with activation profiles of circulating T follicular helper 1 (cTFH1) cells at the acute response strongly correlating with total change of antibody vaccine titers induced by vaccination
We described an increase in activated (PD1+ICOS+) cTFH1 cells (CD4+CXCR3+CXCR5+) at 7 d postvaccination, and these correlated with the rise in antibody-secreting cells (ASCs) and hemagglutinin inhibition titer (HAI) titers, indicating a robust vaccine response [9]
Given that influenza vaccination is recommended for every individual >6 mo old, it is important to understand the immune responses induced by vaccination as additional measures of vaccine efficacy, especially in specific high-risk groups, including Indigenous Australians

Summary

Introduction

High morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in specific high-risk population groups, including children, the elderly, pregnant women, Indigenous people globally, and individuals with underlying comorbidities such as diabetes, immunosuppression, and lung and heart disease [1,2,3]. Vaccine effectiveness differs between seasons and between vaccine components, with H3N2 showing the lowest overall vaccine effectiveness and H1N1pdm (pH1N1) the highest [5] Several factors such as preexisting immunity, immunosenescence, and vaccine strain mismatch can influence vaccine effectiveness [6]. We found robust antibody responses to influenza vaccination induced in Indigenous Australians, with activation profiles of cTFH1 cells at the acute response strongly correlating with total change of antibody vaccine titers induced by vaccination. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and subsequent complications

Methods

Results

Conclusion