High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge.
A comprehensive proteomic screening technology was previously used to characterize T cell responses to Chlamydia trachomatis infection. In this study, we demonstrated that T cells specific for protein antigens identified through this comprehensive technology home to the site of infection after mucosal challenge with C. trachomatis. In addition, T cell responses to these proteins were elicited in multiple genetic backgrounds. Two protein antigens, CT823 and CT144, were evaluated as vaccine candidates. When administered with AbISCO-100 adjuvant, these antigens stimulated potent CD8(+) T cell responses, polyfunctional T(H)1-polarized CD4(+) T cell responses, and high titer protein-specific T(H)1-skewed antibody responses. Vaccination with either antigen with AbISCO-100 provided long-lived protection against intravaginal challenge with C. trachomatis. Adoptive transfer of immune T cells also conferred protection in the challenge model whereas passive transfer of immune serum did not, indicating the critical role for T cell responses in control of this infection. The ability of these antigens to induce potent immune responses and provide long-lived protection in response to challenge provides a basis for the rational design of a C. trachomatis subunit vaccine.
Genocea Biosciences, Inc., 161 First Street, Cambridge, MA 02142, United States.
Michele D
MD
Picard
Kenya Prince
KP
Cohane
Todd M
TM
Gierahn
Darren E
DE
Higgins
Jessica Baker
JB
Flechtner
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D040901:Proteomics; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014621:Vagina / Q000276:immunology* / Q000382:microbiology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D011994:Recombinant Proteins