(American Association for the Advancement of Science (AAAS), 2015) Stary, Georg; Olive, A; Radovic-Moreno, A. F.; Gondek, D.; Alvarez, David; Basto, P. A.; Perro, M.; Vrbanac, Vladimir; Tager, Andrew Martin; Shi, Jinjun; Yethon, J. A.; Farokhzad, Omid; Langer, Robert; Starnbach, Michael; von Andrian-Werburg, Ulrich
Genital 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.
