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Abstract
We reported that intranasal immunization of mice with recombinant major outer membrane protein (MOMP) of Chlamydia trachomatis genetically fused with modified cholera toxin elicited mucosal and systemic antibody responses, but with inefficient protective mechanisms for complete protection of mice against a homologous C. trachomtis challenged infection. To begin to identify specific immunogenic MOMP regions to pursue as vaccine candidates, herein we selected small gene fragments of the MOMP gene containing T-cell epitopes (278-370 aa) and generated a rMOMP peptide (rMOMP-278). rMOMP and rMOMP-278 proteins were cloned, expressed, and their purities and specificities confirmed by SDS-PAGE and Western blot, respectively. We tested the immunogenicity of rMOMP-278 as compared to the parent rMOMP in mice. Mice were immunized intramuscularly with purified rMOMP proteins; total- and isotype- (IgA, IgG1, IgG2a, and IgG2b) specific antibodies in sera and vaginal washes were measured by ELISA. Immunized mice developed antigen-specific total antibodies in a kinetic fashion, with responses being higher to rMOMP than rMOMP- 278. However, antigen-specific isotype antibodies were detected in the order of IgG2b > IgG2a > IgG1 for rMOMP- 278, indicating more of a mixed Th1/Th2 response. Contrastingly, antibody responses to rMOMP was more of a predominant Th2 response in the order of IgG1 > IgG2b > IgG2a. Our data are evidence to suggest that rMOMP-278 is immunogenic by its ability to evoke systemic and mucosal immune responses with a Th1 bias in mice, and therefore may be an attractive peptide alternative to full MOMP as a vaccine candidate against C. trachomatis genital tract infection.
Highlights
Chlamydia trachomatis, an obligate intracellular Gramnegative bacterium, is the leading cause of bacterial sexually transmitted infections (STIs) in the world
We showed that rMOMP genetically linked to modified cholera toxin was immunogenic in mice, with partial protection being afforded after a homologous challenge infection
The findings from this study clearly demonstrate that the intramuscular administration of rMOMP-278 in the absence of an adjuvant can induce significant mucosal and systemic antibody responses with a Th1 bias, in some instances, being as robust as those induced by rMOMP in mice
Summary
An obligate intracellular Gramnegative bacterium, is the leading cause of bacterial sexually transmitted infections (STIs) in the world. Genital tract infection with C. trachomatis, poses a significant risk in women, often leading to chronic abdominal pain, pelvic inflammatory disease (PID), fallopian tube scarring, ectopic pregnancy, and infertility. Effective antimicrobials are available for Chlamydia, this approach has been unsuccessful in curtailing the spread of infections because the latter are frequently asymptomatic. Such insidious infections make diagnosis and application of antibiotic therapy late and ineffective. Development of a safe efficacious prophylactic mucosal vaccine for C. trachomatis is the key to reduce its transmission. To date, no efficacious vaccine against this human pathogen is available
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