title: Chlamydia muridarum T cell antigens and adjuvants that induce protective immunity in mice.
abstract: Major impediments to a Chlamydia vaccine lie in discovering T cell antigens and polarizing adjuvants that stimulate protective immunity. We previously reported the discovery of three T cell antigens (PmpG, PmpF, and RplF) via immunoproteomics that elicited protective immunity in the murine genital tract infection model against Chlamydia infection after adoptive transfer of antigen-pulsed dendritic cells. To expand the T cell antigen repertoire necessary for a Chlamydia vaccine, we evaluated 10 new Chlamydia T cell antigens discovered via immunoproteomics in addition to the 3 antigens reported earlier as a molecular subunit vaccine. We first tested five adjuvants, including three cationic liposome formulations (dimethyldioctadecylammonium bromide-monophosphoryl lipid A [DDA-MPL], DDA-trehalose 6,6'-dibehenate [DDA-TDB {CAF01}], and DDA-monomycolyl glycerol [DDA-MMG {CAF04}]), Montanide ISA720-CpG-ODN1826, and alum using the PmpG protein as a model T cell antigen in the mouse genital tract infection model. The results showed that the cationic liposomal adjuvants DDA-MPL and DDA-TDB elicited the best protective immune responses, characterized by multifunctional CD4(+) T cells coexpressing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), and reduced infection by more than 3 logs. Using DDA-MPL as an adjuvant, we found that 7 of 13 Chlamydia T cell antigens (PmpG, PmpE, PmpF, Aasf, RplF, TC0420, and TC0825) conferred protection better than or equal to that of the reference vaccine antigen, major outer membrane protein (MOMP). Pools of membrane/secreted proteins, cytoplasmic proteins, and hypothetical proteins were tested individually or in combination. Immunization with combinations protected as well as the best individual protein in that combination. The T cell antigens and adjuvants discovered in this study are of further interest in the development of a molecularly defined Chlamydia vaccine.
authors.affiliation: British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Karuna P
authors.initials: KP
authors.lastname: Karunakaran
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Jiang
authors.forename: Caixia
authors.initials: C
authors.lastname: Shen
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology* / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology / Q000517:prevention & control; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008050:Lipid A / Q000276:immunology; D055666:Lipopeptides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018272:Porins / Q000276:immunology; D000644:Quaternary Ammonium Compounds / Q000276:immunology; D060737:Reproductive Tract Infections / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D008050:Lipid A; D055666:Lipopeptides; D018272:Porins; D000644:Quaternary Ammonium Compounds; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; C071677:omp1 protein, Chlamydia trachomatis; C015831:dimethyldioctadecylammonium; D007371:Interferon-gamma