A mucosal vaccine against <i>Chlamydia trachomatis</i> generates two waves of protective memory T cells

Georg Stary(Harvard University), Andrew J. Olive(Harvard University), Aleksandar F. Radovic‐Moreno(Harvard–MIT Division of Health Sciences and Technology), David Gondek(Harvard University), David Álvarez(Harvard University), Pamela A. Basto(Harvard–MIT Division of Health Sciences and Technology), Mario Perro(Harvard University), Vladimir Vrbanac(Harvard University), Andrew M. Tager(Harvard University), Jinjun Shi(Brigham and Women's Hospital), Jeremy A. Yethon(Sanofi (United States)), Omid C. Farokhzad(Brigham and Women's Hospital), Róbert Langer(Harvard–MIT Division of Health Sciences and Technology), Michael N. Starnbach(Harvard University), Ulrich H. von Andrian(Harvard University)
Science
June 18, 2015
10.1126/science.aaa8205
Cited by 369Open Access
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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 (T(RM) cells). Optimal Ct clearance required both T(RM) 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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