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bioRxiv · 10.1101/2020.11.25.398651

Mucosal vaccination with cyclic-di-nucleotide adjuvants induces effective T cell homing and IL-17 dependent protection against M. tuberculosis infection

Jong, R. M.·Van Dis, E.·Nguyenla, X.·Baltodano, A.·Pastenkos, G.·Xu, C.·Yosef, N.·McWhirter, S.·Stanley, S.
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Abstract

The only licensed vaccine for tuberculosis, Mycobacterium bovis Bacille Calmette-Guerin (BCG), is not reliably effective against adult pulmonary tuberculosis. A major hurdle to tuberculosis vaccine development is incomplete understanding of successful immunity against the causative agent Mycobacterium tuberculosis. Recently, we demonstrated that a protein subunit vaccine adjuvanted with STING-activating cyclic-di-nucleotides (CDNs) robustly protects against tuberculosis infection in mice. Here we show mucosal vaccination with this vaccine induces production of T cells that home to lung parenchyma and penetrate lesions in the lung. Protection is partially dependent on IL-17, type I interferon (IFN), and IFN-{gamma}, while the transcription factor STAT-6 is dispensable. Single cell transcriptomics reveals mucosal vaccination with a CDN vaccine increases transcriptional heterogeneity in CD4 cells, including a significant population of non-classical IFN-{gamma} and IL-17 co-expressing Th1-Th17 cells, as well as markers of memory and activation. Th1-Th17 cells in vaccinated mice are enriched for expression of the T cell functional markers Tnfsf8 and Il1r1 relative to more conventional Th1 cells. These data provide critical insight into the immune mediators and diversity of T cell responses that can contribute to vaccine efficacy against M. tuberculosis infection.

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Jong, R. M., Van Dis, E., Nguyenla, X., Baltodano, A., Pastenkos, G., Xu, C., Yosef, N., McWhirter, S., Stanley, S.. 2020-11-27. Mucosal vaccination with cyclic-di-nucleotide adjuvants induces effective T cell homing and IL-17 dependent protection against M. tuberculosis infection. https://doi.org/10.1101/2020.11.25.398651

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