CTH522/CAF01 vaccination elicits clonally related Th17 subsets that mediate IL-17A-dependent protection against Chlamydia trachomatis.

Authors

Nina Dieu Nhien Tran Nguyen, Safia Guleed, Sharmila Subratheepam, Ernesto Marcos-Lopez, Matthieu Van Tilbeurgh, Marco Leonec, Anne-Sophie Galloüet, Katharina Wørzner, Joshua Woodworth, Thomas Lindenstrøm, Kristoffer Mazanti Melchiors, Tu Hu, Søren Hallstrøm, Roger Le Grand, Gabriel Kristian Pedersen, Rasmus Mortensen, Jan Pravsgaard Christensen, Frank Follmann, Jes Dietrich

Published in

Journal of immunology (Baltimore, Md. : 1950). Volume 215. Issue 10. Oct 01, 2026.

Abstract

Chlamydia trachomatis is the leading bacterial sexually transmitted pathogen worldwide and a major cause of reproductive tract disease, highlighting the need for an effective vaccine. Defining the immune mechanisms underlying vaccine-induced protection is therefore critical. We previously demonstrated that in mice vaccinated with CTH522/CAF01, genital tract Th17 cells correlated with protection against both infection and pathology. In this study, we further characterized these vaccine-induced Th17 cells in an infected genital tract. Fate-mapping and single-cell transcriptomic analyses revealed that CTH522/CAF01 vaccination generated multiple Th17-derived subsets, including a large memory-like population as well as effector Th17 and Th17-derived Th1-like subsets. These subsets shared common TCR clonotypes, and RNA velocity analyses predicted a unified differentiation trajectory, with one precursor population seeding both effector lineages. Our findings demonstrate a high degree of plasticity within the Th17 population and reveals previously uncharacterized Th17 subsets present during infection with C. trachomatis. Functional studies demonstrated that the Th17 subset that produced IL-17A was essential for early bacterial control, whereas IFN-γ-producing Th1 cells and Th17-derived Th1-like cells were not. Collectively, our findings provide mechanistic insight into Th17 biology and redefine the importance of IL-17A producing Th17 cells in early vaccine-mediated protection against C. trachomatis.

PMID:
42823065
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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