1. Lung IL-17A-Producing CD4+ T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines
- Author
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Erica L. Stewart, Claudio Counoupas, Diana H. Quan, Trixie Wang, Nikolai Petrovsky, Warwick J. Britton, and James A. Triccas
- Subjects
tuberculosis ,vaccine ,adjuvant ,mucosal ,Th17 ,IL-17A ,Medicine - Abstract
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.
- Published
- 2024
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