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

Anja Weinreich Olsen,Jan Pravsgaard Christensen,Nina Dieu Nhien Tran Nguyen,Safia Guleed,Jes Dietrich,Frank Follmann

doi:10.3389/fimmu.2021.790463

Anja Weinreich Olsen, Jan Pravsgaard Christensen + Show 4 more

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https://doi.org/10.3389/fimmu.2021.790463

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Abstract

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.

Highlights

Chlamydia trachomatis (C.t.) is the most common sexually transmitted bacterium with an estimated 127 million new cases occurring every year globally [1]
We recently showed that a parenteral vaccine inducing only systemic immunity, given prior to the first infection, induced protective systemic Th1/Th17 T cell immunity that could be measured between day 3 and 7 post infection [15]
In contrast to day 3 post the infection no. 1 (PI-1) which is shown in Figure 4, we found that at day 3 post infection no. 2 (PI-2), the percentage of CD4 T cells in the genital tract (GT) was similar in the SC and SIM groups (20.8% in SC animals and 18.9% in SIM animals) (Figure 5)

Summary

Introduction

Chlamydia trachomatis (C.t.) is the most common sexually transmitted bacterium with an estimated 127 million new cases occurring every year globally [1]. C.t. is an obligate intracellular bacterium infecting both men and women. Genital infections are frequently asymptomatic and left untreated. Untreated women can experience serious sequelae such as pelvic inflammatory disease that. As repeated infections with C.t. are not uncommon [5], it has become clear that the goal of a vaccine against Chlamydia is to prevent a first infection, and subsequent infections. To develop such a vaccine, a better understanding of the most optimal protective immune response is required

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