A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells
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Langer_A mucosal.pdf
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Author(s)
Stary, George
Olive, Andrew J.
Radovic-Moreno, Aleksandar F.
Gondek, David
Alvarez, David
Basto, Pamela A.
Perro, Mario
Vrbanac, Vladimir D.
Tager, Andrew M.
Shi, Jinjun
Date Issued
June 2015
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Stary, G., A. Olive, A. F. Radovic-Moreno, D. Gondek, D. Alvarez, P. A. Basto, M. Perro, et al. “A Mucosal Vaccine Against Chlamydia Trachomatis Generates Two Waves of Protective Memory T Cells.” Science 348, no. 6241 (June 18, 2015): aaa8205–aaa8205.
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Author's final manuscript
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[superscript +]CD103[superscript –] dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b[superscript –]CD103[superscript +] 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[subscript RM] cells). Optimal Ct clearance required both T[subscript 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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1126/science.aaa8205
