title: Identification and characterization of novel recombinant vaccine antigens for immunization against genital Chlamydia trachomatis.
abstract: Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide, with over 91 million cases estimated annually. An effective subunit vaccine against Chlamydia may require a multivalent subunit cocktail of antigens in a single formulation for broad coverage of a heterogeneous major histocompatibility complex population. Herein, we describe the identification of novel C. trachomatis antigens by CD4+ and CD8+ T-cell expression cloning, serological expression cloning, and an in silico analysis of the C. trachomatis genome. These antigens elicited human CD4+ T-cell responses, and a subset proved to be immunogenic and protective when administered as immunoprophylactic vaccines against C. trachomatis challenge. Candidate vaccines consisting of the prioritized C. trachomatis antigens adjuvanted in a GlaxoSmithKline proprietary AS01B adjuvant were prioritized based on induction of solid protection against challenge in C57BL/6 and BALB/c mice with C. trachomatis. Some of the vaccines prevented bacterial shedding and colonization of the upper genital tract to varying degrees by mechanisms that may include CD4+ T cells.
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98104, USA. rcoler@idri.org
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatia
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Maisonneuve
authors.forename: Peter
authors.initials: P
authors.lastname: Probst
authors.forename: Brenda
authors.initials: B
authors.lastname: Barth
authors.forename: Pamela
authors.initials: P
authors.lastname: Ovendale
authors.forename: Hang
authors.initials: H
authors.lastname: Fang
authors.forename: Mark
authors.initials: M
authors.lastname: Alderson
authors.forename: Yves
authors.initials: Y
authors.lastname: Lobet
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic