A novel recombinant multisubunit vaccine against Chlamydia.
The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues. We investigated the hypothesis that rVCG could serve as effective delivery vehicles for single or multiple subunit chlamydial vaccines to induce a high level of protective immunity. rVCG-expressing chlamydial outer membrane proteins were produced by a two-step genetic process, involving cloning of Omp genes in V. cholerae, followed by gene E-mediated lysis of the cells. The immunogenicity and vaccine efficacy of rVCG-expressing single and multiple subunits were compared. Immunologic analysis indicated that i.m. immunization of mice with either vaccine construct induced a strong mucosal and systemic specific Th1 response against the whole chlamydial organism. However, there was an immunogenic advantage associated with the multiple subunit vaccine that induced a higher frequency of Th1 cells and a relatively greater ability to confer protective immunity, compared with the single subunit construct. These results support the operational theory that the ability of a vaccine to confer protective immunity against Chlamydia is a function of the level of Th1 response elicited.
Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA. feko@msm.edu
Francis O
FO
Eko
Qing
Q
He
Teresa
T
Brown
Lucinda
L
McMillan
Godwin O
GO
Ifere
Godwin A
GA
Ananaba
Deborah
D
Lyn
Werner
W
Lubitz
Kathryn L
KL
Kellar
Carolyn M
CM
Black
Joseph U
JU
Igietseme
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D002689:Chlamydia / Q000235:genetics / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D005822:Genetic Vectors; D051379:Mice; D010957:Plasmids; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
D001425:Bacterial Outer Membrane Proteins; D014614:Vaccines, Synthetic