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

Tuberculosis (TB), caused by , 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 . 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 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 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 and suggests that mucosal immune profiles should be explored for novel CoP.