Identification and characterization of novel recombinant vaccine antigens for immunization against genital Chlamydia trachomatis.
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.
Coler
Rhea N
RN
Infectious Disease Research Institute, Seattle, WA 98104, USA. rcoler@idri.org
Bhatia
Ajay
A
Maisonneuve
Jean-Francois
JF
Probst
Peter
P
Barth
Brenda
B
Ovendale
Pamela
P
Fang
Hang
H
Alderson
Mark
M
Lobet
Yves
Y
Cohen
Joe
J
Mettens
Pascal
P
Reed
Steven G
SG
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
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic