Immunogenicity and protection against genital Chlamydia infection and its complications by a multisubunit candidate vaccine
Godwin O. Ifere, Qing He, Joseph U. Igietseme, Godwin A. Ananaba, Deborah Lyn, Werner Lubitz, Kathryn L. Kellar, Carolyn M. Black, Francis O. Eko
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta; National Center for Infectious Disease, Centers for Disease Control and Prevention, Atlanta; Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, United States; and Institute of Microbiology and Genetics, University of Vienna, Vienna, Austria
Received: May 29, 2006 Revised: September 20, 2006 Accepted: October 2, 2006
Background and purpose:
Genital infections due to Chlamydia trachomatis pose a considerable public health challenge worldwide and a vaccine is urgently needed to protect against these infections. We examined whether a vaccine composed of a combination of the major outer membrane protein (MOMP) and porin B protein (PorB) of C. trachomatis would have a protective advantage over a single subunit construct.
Single and multisubunit vaccines expressing MOMP and PorB were constructed and evaluated in the mouse model of genital infection. Thus, groups of female C57BL/6 mice were immunized intramuscularly with recombinant Vibrio cholerae ghosts (VCG) expressing the vaccine antigens or VCG alone and humoral and cell-mediated immune responses were evaluated.
Significant levels of Chlamydia-specific secretory immunoglobulin A and immunoglobulin G2a were detected in vaginal washes and serum of immunized mice. The multisubunit construct induced a significantly higher level of T-helper Type 1 response than the single subunits as measured by the amount of interferon-gamma produced by immune T cells in response to re-stimulation with ultraviolet-irradiated elementary bodies in vitro. Three weeks after the last immunization, animals were challenged intravaginally with 107 inclusion-forming units of C. trachomatis serovar D. There was a significant difference in the intensity and duration of vaginal shedding between the vaccine-immunized mice and controls. All the animals immunized with the multisubunit vaccine had completely resolved the infection 2 weeks post-challenge. Higher numbers of embryos were observed in vaccinated animals than in controls, indicating protection against infertility.
These results underscore the potential, albeit moderate, vaccine advantage of the multisubunit formulation.
Bacterial outer membrane proteins; Bacterial vaccines; Chlamydia infections; Porins; Vaccination
J Microbiol Immunol Infect. 2007;40:188-200.