Lung IL-17A-Producing CD4+ T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines.
Vaccines (Basel)
; 12(2)2024 Jan 26.
Article
in En
| MEDLINE
| ID: mdl-38400112
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Vaccines (Basel)
Year:
2024
Type:
Article
Affiliation country:
Australia