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

Stewart, EL; Counoupas, C; Quan, DH; Wang, T; Petrovsky, N; Britton, WJ; Triccas, JA

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

Stewart, EL Counoupas, C Quan, DH Wang, T Petrovsky, N Britton, WJ Triccas, JA

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Vaccines, 2024, 12, (2), pp. 128
Issue Date:: 2024-01-26

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Field	Value	Language
dc.contributor.author	Stewart, EL
dc.contributor.author	Counoupas, C
dc.contributor.author	Quan, DH
dc.contributor.author	Wang, T
dc.contributor.author	Petrovsky, N
dc.contributor.author	Britton, WJ
dc.contributor.author	Triccas, JA
dc.date.accessioned	2025-01-28T06:01:42Z
dc.date.available	2024-01-20
dc.date.available	2025-01-28T06:01:42Z
dc.date.issued	2024-01-26
dc.identifier.citation	Vaccines, 2024, 12, (2), pp. 128
dc.identifier.issn	2076-393X
dc.identifier.issn	2076-393X
dc.identifier.uri	http://hdl.handle.net/10453/184423
dc.description.abstract	Tuberculosis (TB), caused by i Mycobacterium tuberculosis /i , 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 i M. tuberculosis /i . 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 i M. tuberculosis /i in mouse models, was combined with either Advax sup /sup 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 i M. tuberculosis /i infection. Although considered essential for the control of mycobacteria, induction of IFN- -expressing CD4 sup + /sup T cells in the blood or lungs did not correlate with protection. Instead, CD4 sup + /sup T cells in the lungs expressing IL-17A correlated with reduced bacterial burden. This study identified pulmonary IL-17A-expressing CD4 sup + /sup T cells as a CoP against i M. tuberculosis /i and suggests that mucosal immune profiles should be explored for novel CoP.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation	http://purl.org/au-research/grants/nhmrc/1153493
dc.relation.ispartof	Vaccines
dc.relation.isbasedon	10.3390/vaccines12020128
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	3204 Immunology
dc.subject.classification	3207 Medical microbiology
dc.title	Lung IL-17A-Producing CD4+ T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
utslib.copyright.status	open_access	*
pubs.consider-herdc	true
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-01-28T06:01:39Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	2

Abstract:

Tuberculosis (TB), caused by i Mycobacterium tuberculosis /i , 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 i M. tuberculosis /i . 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 i M. tuberculosis /i in mouse models, was combined with either Advax sup /sup 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 i M. tuberculosis /i infection. Although considered essential for the control of mycobacteria, induction of IFN- -expressing CD4 sup + /sup T cells in the blood or lungs did not correlate with protection. Instead, CD4 sup + /sup T cells in the lungs expressing IL-17A correlated with reduced bacterial burden. This study identified pulmonary IL-17A-expressing CD4 sup + /sup T cells as a CoP against i M. tuberculosis /i and suggests that mucosal immune profiles should be explored for novel CoP.

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http://hdl.handle.net/10453/184423