title: 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-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.
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Stary
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Olive
authors.affiliation: Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Aleksandar F
authors.initials: AF
authors.lastname: Radovic-Moreno
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gondek
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.affiliation: Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Basto
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Perro
authors.affiliation: The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Vladimir D
authors.initials: VD
authors.lastname: Vrbanac
authors.affiliation: The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Sanofi Pasteur, Cambridge MA 02139, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Yethon
authors.affiliation: 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.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.affiliation: Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.|The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018845:CD11 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000528:radiation effects; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D053758:Nanoparticles / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014466:Ultraviolet Rays; D014599:Uterus / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D001428:Bacterial Vaccines; D018845:CD11 Antigens; D039001:Integrin alpha Chains; D015164:Vaccines, Inactivated; C091367:alpha E integrins