Ithaca College

Georg Stary, Andrew Olive, Aleksandar F. Radovic-Moreno, David Gondek, David Alvarez, Pamela A. Basto, Mario Perro, Vladimir D. Vrbanac, Andrew M. Tager, Jinjun Shi, Jeremy A. Yethon, Omid C. Farokhzad, Robert Langer, Michael N. Starnbach, Ulrich H. von Andrian. (2015). A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells. Science (348) 6241. DOI: 10.1126/science.aaa8205.

Abstract

Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ–producing CD4 T cells. By contrast, we report that 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 (cSAPs) 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 cells). 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.