Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis .

Autor:	Nguyen NDNT; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Guleed S; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Olsen AW; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Follmann F; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Christensen JP; Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark., Dietrich J; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Dec 02; Vol. 12, pp. 790463. Date of Electronic Publication: 2021 Dec 02 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.790463
Abstrakt:	The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add to the protection mediated by circulating immunity. Out of several mucosal vaccine strategies, a strategy termed SIM (for simultaneous intrauterine and parenteral immunization with CAF01 adjuvanted CTH522), was superior in generating genital tract tissue-resident Th1/Th17 T cell immunity. This led to a faster and stronger local CD4 T cell response post infection, consisting of multifunctional IFNγ/TNFα-producing Th1 T cells and IFNγ/TNFα/IL-17-producing Th17 T cells, and a faster recruitment of innate immune cells. Post infection, SIM animals showed an additional significant reduction in bacterial levels compared to mice having received only a parenteral vaccine. Nevertheless, the parenteral strategy reduced bacterial levels by 75%, and interestingly, post infection, these mice generated their own vaccine-derived genital tract tissue-resident memory Th1/Th17 T cells, which upon a subsequent infection showed as fast an activation in the genital tract, as observed in SIM mice. Furthermore, in contrast to after the first infection, both groups of mice now showed a similar infection-induced boost in local vaginal IgA and IgG titers. Thus, vaccine-induced resident immunity, generated pre-infection, led to an advantage in the response against the first infection, but not the second infection, suggesting that a parenteral vaccine strategy is a suitable vaccine strategy against infections with Chlamydia trachomatis . Competing Interests: AWO and FF are co-inventors on a patent application on vaccines against chlamydia [WO2014146663A1]. All rights have been assigned to Statens Serum Institut, a Danish not-for-profit institute under the Ministry of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Nguyen, Guleed, Olsen, Follmann, Christensen and Dietrich.)
Databáze:	MEDLINE
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