A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells
Radovic-Moreno, A. F.
Basto, P. A.
Vrbanac, V. D.
Yethon, J. A.
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CitationStary, G., A. Olive, A. F. Radovic-Moreno, D. Gondek, D. Alvarez, P. A. Basto, M. Perro, et al. 2015. “A Mucosal Vaccine Against Chlamydia Trachomatis Generates Two Waves of Protective Memory T Cells.” Science 348 (6241) (June 18): aaa8205–aaa8205. doi:10.1126/science.aaa8205.
AbstractGenital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ producing CD4 T-cells. By contrast, mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T-cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAP) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b+CD103− dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b−CD103+ DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T-cells, but only mucosal vaccination induced effector T-cells that rapidly seeded uterine mucosa with resident memory T-cells (TRM). Optimal Ct clearance required both TRM seeding and subsequent infection-induced recruitment of circulating memory T-cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T-cell subsets with distinct migratory properties.
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