A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells

作者：Stary Georg; Olive Andrew; Radovic Moreno Aleksandar F; Gondek David; Alvarez David; Basto Pamela A; Perro Mario; Vrbanac Vladimir D; Tager Andrew M; Shi Jinjun; Yethon Jeremy A; Farokhzad Omid C; Langer Robert; Starnbach Michael N; von Andrian Ulrich H^*

来源：Science, 2015, 348(6241): aaa8205.

DOI：10.1126/science.aaa8205

Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-g-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 (T-RM 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.

• 出版日期2015-6-19