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

ABSTRACT: Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-?-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.

SUBMITTER: Stary G

PROVIDER: S-EPMC4605428 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Stary Georg G Olive Andrew A Radovic-Moreno Aleksandar F AF Gondek David D Alvarez David D Basto Pamela A PA Perro Mario M Vrbanac Vladimir D VD Tager Andrew M AM Shi Jinjun J Shi Jinjun J Yethon Jeremy A JA Farokhzad Omid C OC Langer Robert R Starnbach Michael N MN von Andrian Ulrich H UH

Science (New York, N.Y.) 20150601 6241

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 immunogen ...[more]

PMID: 26089520

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Project description:Chlamydia trachomatis causes respiratory and sexually transmitted infections. Here, we tested a vaccine formulated with the recombinant major outer membrane protein from C. trachomatis mouse pneumonitis (CT-MoPn) for its ability to protect mice against an intranasal (i.n.) challenge. The adjuvants CpG and Montanide were used for systemic routes, intramuscular (i.m.) and subcutaneous (s.c.), and cholera toxin for mucosal routes, sublingual (s.l.) and colonic (c.l.). Mucosal immunizations were performed either alone or in combination with systemic routes. Mice inoculated i.n. with 10(4) inclusion-forming units (IFU) of CT-MoPn served as a positive control and the Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) as the negative antigen control. Immunized animals were challenged i.n. with 10(4)IFU of CT-MoPn. Following immunization the combination groups showed high chlamydial serum IgG titers (s.l.+i.m.+s.c. 25,600; c.l+i.m.+s.c. 102,400) and the IgG2a/IgG1 ratios indicated a Th1 response. Following the i.n. challenge the s.l.+i.m.+s.c. group showed the best protection as demonstrated by an increase in body weight of 0.3% over the 10 day course of infection. A statistically significant difference was found when compared with the Ng-rPorB immunized animals that had lost 20% of their original body weight (P<0.05). In addition, the repeated measures ANOVA test showed significant difference in body weight change for the combined immunized groups vs their mucosal counterparts and also the systemic immunized group. A statistically significant difference (P<0.05) was also observed in the number of IFUs recovered from the lungs when the s.l.+i.m.+s.c. (2.8×10(6)) and c.l.+i.m.+s.c. (3.4×10(6)) groups were compared to their respective mucosal only groups (s.l.: 61.9×10(6) and c.l: 136.2×10(6)) and the control Ng-rPorB immunized mice (198.2×10(6)) (P<0.05). In conclusion, a combined systemic plus mucosal vaccination provides better protection against a respiratory challenge with C. trachomatis than either systemic or mucosal immunizations alone.

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

Publications

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

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