A Novel Recombinant Multisubunit Vaccine against Chlamydia

• Published in: The Journal of immunology (1950) Vol. 173; no. 5; pp. 3375 - 3382
• Main Authors: Eko, Francis O, He, Qing, Brown, Teresa, McMillan, Lucinda, Ifere, Godwin O, Ananaba, Godwin A, Lyn, Deborah, Lubitz, Werner, Kellar, Kathryn L, Black, Carolyn M, Igietseme, Joseph U
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.09.2004
• Subjects: Animals; Antibody Formation - immunology; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Chlamydia - genetics; Chlamydia - immunology; Chlamydia Infections - immunology; Chlamydia Infections - prevention & control; Genetic Vectors; Mice; Plasmids; Th1 Cells - immunology; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.5.3375

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.