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

The right combination for protectionDespite its prevalence, no vaccine exists to protect against infection with the sexually transmitted bacterium Chlamydia trachomatis. Stary et al. now report on one potential vaccine candidate (see the Perspective by Brunham). Vaccinating with an ultraviolet light...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 2015-06, Vol.348 (6241), p.1331-1331
Hauptverfasser: 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.
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Sprache:eng
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Zusammenfassung:The right combination for protectionDespite its prevalence, no vaccine exists to protect against infection with the sexually transmitted bacterium Chlamydia trachomatis. Stary et al. now report on one potential vaccine candidate (see the Perspective by Brunham). Vaccinating with an ultraviolet light-inactivated C. trachomatis linked to adjuvant-containing charged nanoparticles protected female conventional and humanized mice against C. trachomatis infection. The vaccine conferred protection only when delivered through mucosal routes. Protection relied on targeting the bacteria to a particular population of immunogenic dendritic cells and inducing memory T cells that resided in the female genital tract.Science, this issue 10.1126/science.aaa8205; see also p. 1322 Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon- gamma -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 (TRM 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaa8205