Lung IL-17A-Producing CD4 + T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines.

Autor: Stewart EL; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia., Counoupas C; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia., Quan DH; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; Centre for Inflammation, School of Life Sciences, Faculty of Science, The University of Technology Sydney, Ultimo, NSW 2007, Australia., Wang T; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia., Petrovsky N; Vaxine Pty Ltd., Warradale, Adelaide, SA 5046, Australia., Britton WJ; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia., Triccas JA; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.; Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
Jazyk: angličtina
Zdroj: Vaccines [Vaccines (Basel)] 2024 Jan 26; Vol. 12 (2). Date of Electronic Publication: 2024 Jan 26.
DOI: 10.3390/vaccines12020128
Abstrakt: Tuberculosis (TB), caused by Mycobacterium tuberculosis , results in approximately 1.6 million deaths annually. BCG is the only TB vaccine currently in use and offers only variable protection; however, the development of more effective vaccines is hindered by a lack of defined correlates of protection (CoP) against M. tuberculosis . Pulmonary vaccine delivery is a promising strategy since it may promote lung-resident immune memory that can respond rapidly to respiratory infection. In this study, CysVac2, a subunit protein previously shown to be protective against M. tuberculosis in mouse models, was combined with either Advax ® adjuvant or a mixture of alum plus MPLA and administered intratracheally into mice. Peripheral immune responses were tracked longitudinally, and lung-local immune responses were measured after challenge. Both readouts were then correlated with protection after M. tuberculosis infection. Although considered essential for the control of mycobacteria, induction of IFN-γ-expressing CD4 + T cells in the blood or lungs did not correlate with protection. Instead, CD4 + T cells in the lungs expressing IL-17A correlated with reduced bacterial burden. This study identified pulmonary IL-17A-expressing CD4 + T cells as a CoP against M. tuberculosis and suggests that mucosal immune profiles should be explored for novel CoP.
Databáze: MEDLINE
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