Evaluation of a broadly protective Chlamydia –cholera combination vaccine candidate

• Published in: Vaccine 2011-05, Vol.29 (21), p.3802-3810
• Main Authors: Eko, F.O, Okenu, D.N, Singh, U.P, He, Q, Black, C, Igietseme, J.U
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; animal pathogens; Animals; Antibodies, Bacterial - blood; Antibody Formation; Applied microbiology; Bacterial Proteins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Chlamydia; Chlamydia Infections - immunology; Chlamydia Infections - prevention & control; Chlamydia muridarum; Chlamydia trachomatis; Chlamydia trachomatis - immunology; Cholera; Cholera - immunology; Cholera - prevention & control; Combination vaccine; Cross Protection; Cytokines - immunology; Drug Evaluation; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; humans; humoral immunity; immunization; Membrane Proteins - immunology; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; porins; Porins - immunology; serotypes; vaccine development; vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Combined - administration & dosage; Vaccines, Combined - immunology; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Vibrio cholerae; Vibrio cholerae - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.03.027

Abstract The need to simultaneously target infections with epidemiological overlap in the population with a single vaccine provides the basis for developing combination vaccines. Vibrio cholerae ghosts (rVCG) offer an attractive approach for developing vaccines against a number of human and animal pathogens. In this study, we constructed a multisubunit vaccine candidate co-expressing the serovar D-derived Porin B and polymorphic membrane protein-D proteins of Chlamydia trachomatis and evaluated its ability to simultaneously induce broad-based chlamydial immunity and elicit a vibriocidal antibody response to the Vibrio carrier envelope. Intramuscular (IM) immunization with the vaccine candidate elicited high levels of antigen-specific genital mucosal and systemic Th1 cell-mediated and humoral immune responses against heterologous serovars and strains, including serovars E–H and L. Also, in addition to the multisubunit vaccine, the single subunit constructs conferred significant cross protection against the heterologous mouse strain, Chlamydia muridarum . Furthermore, all mice immunized with rVCG vaccine constructs responded with a significant rise in vibriocidal antibody titer, the surrogate marker for protection in cholera. These findings demonstrate the ability of the multisubunit vaccine to induce cross protective chlamydial as well as vibriocidal immunity and establish the possibility of developing a broadly efficacious Chlamydia –cholera combination vaccine.