Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines
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 corr...
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MDPI AG
2024-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/2/128 |
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| author | Erica L. Stewart Claudio Counoupas Diana H. Quan Trixie Wang Nikolai Petrovsky Warwick J. Britton James A. Triccas |
| author_facet | Erica L. Stewart Claudio Counoupas Diana H. Quan Trixie Wang Nikolai Petrovsky Warwick J. Britton James A. Triccas |
| author_sort | Erica L. Stewart |
| collection | DOAJ |
| description | 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-γ-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. |
| first_indexed | 2024-03-07T22:11:36Z |
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| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-07T22:11:36Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-f4b0819b5c944be49480f1bf7d8e91f12024-02-23T15:36:55ZengMDPI AGVaccines2076-393X2024-01-0112212810.3390/vaccines12020128Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis VaccinesErica L. Stewart0Claudio Counoupas1Diana H. Quan2Trixie Wang3Nikolai Petrovsky4Warwick J. Britton5James A. Triccas6Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaSydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaCentre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, AustraliaCentre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, AustraliaVaxine Pty Ltd., Warradale, Adelaide, SA 5046, AustraliaCentre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, AustraliaSydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaTuberculosis (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-γ-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.https://www.mdpi.com/2076-393X/12/2/128tuberculosisvaccineadjuvantmucosalTh17IL-17A |
| spellingShingle | Erica L. Stewart Claudio Counoupas Diana H. Quan Trixie Wang Nikolai Petrovsky Warwick J. Britton James A. Triccas Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines Vaccines tuberculosis vaccine adjuvant mucosal Th17 IL-17A |
| title | Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines |
| title_full | Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines |
| title_fullStr | Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines |
| title_full_unstemmed | Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines |
| title_short | Lung IL-17A-Producing CD4<sup>+</sup> T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines |
| title_sort | lung il 17a producing cd4 sup sup t cells correlate with protection after intrapulmonary vaccination with differentially adjuvanted tuberculosis vaccines |
| topic | tuberculosis vaccine adjuvant mucosal Th17 IL-17A |
| url | https://www.mdpi.com/2076-393X/12/2/128 |
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