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Science. 2015 Jun 19;348(6241):aaa8205. doi: 10.1126/science.aaa8205.

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

Author information

1
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA.
3
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
5
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
6
Sanofi Pasteur, Cambridge MA 02139, USA.
7
King Abdulaziz University, Jeddah, Saudi Arabia.
8
The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
#
Contributed equally

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.

PMID:
26089520
PMCID:
PMC4605428
DOI:
10.1126/science.aaa8205
[Indexed for MEDLINE]
Free PMC Article

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