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

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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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Journal

Journal ID (iso-abbrev): Science

Title: Science (New York, N.Y.)

ISSN (Electronic): 1095-9203

ISSN (Print): 0036-8075

Publication date (Electronic): Jun 19 2015

Volume: 348

Issue: 6241

Affiliations

[1 ] Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu.

[2 ] Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.

[3 ] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

[4 ] 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 ] Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. King Abdulaziz University, Jeddah, Saudi Arabia.

[8 ] Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu.

Article

Publisher Item ID: 348/6241/aaa8205 Mid ID: NIHMS726437

DOI: 10.1126/science.aaa8205

PubMed ID: 26089520

SO-VID: 9568cdbe-4401-4cd9-a703-c92eedd4f786

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