A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells
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 th...
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2016
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| Online Access: | http://hdl.handle.net/1721.1/101205 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826202864993697792 |
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| author | 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 Yethon, Jeremy A. Farokhzad, Omid C. Langer, Robert Starnbach, Michael N. von Andrian, Ulrich H. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology 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 Yethon, Jeremy A. Farokhzad, Omid C. Langer, Robert Starnbach, Michael N. von Andrian, Ulrich H. |
| author_sort | Stary, George |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:22:55Z |
| format | Article |
| id | mit-1721.1/101205 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:22:55Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1012052022-09-28T07:55:29Z A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells 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 Yethon, Jeremy A. Farokhzad, Omid C. Langer, Robert Starnbach, Michael N. von Andrian, Ulrich H. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Radovic-Moreno, Aleksandar F. Basto, Pamela A. Langer, Robert 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. National Institutes of Health (U.S.) (Grant U54-CA119349) National Institutes of Health (U.S.) (Grant U54-CA151884) National Institutes of Health (U.S.) (Grant R37-EB000244) Prostate Cancer Foundation MIT-Portugal Program National Science Foundation (U.S.). Graduate Research Fellowship 2016-02-17T21:52:11Z 2016-02-17T21:52:11Z 2015-06 2015-01 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/101205 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. https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1126/science.aaa8205 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | 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 Yethon, Jeremy A. Farokhzad, Omid C. Langer, Robert Starnbach, Michael N. von Andrian, Ulrich H. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title | A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title_full | A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title_fullStr | A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title_full_unstemmed | A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title_short | A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells |
| title_sort | mucosal vaccine against chlamydia trachomatis generates two waves of protective memory t cells |
| url | http://hdl.handle.net/1721.1/101205 https://orcid.org/0000-0003-4255-0492 |
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