Mucosal immunization with recombinant MOMP genetically linked with modified cholera toxin confers protection against Chlamydia trachomatis infection

Chlamydia trachomatis is a major human health pathogen due to its role in sexually transmitted diseases. Thus, there is a need to develop an effective vaccine at the mucosal surface against this pathogen. In an effort to develop a mucosal vaccine, a modified cholera toxin gene was genetically linked to the C. trachomatis MoPn NiggII MOMP gene to generate a recombinant protein with the mucosal adjuvant properties of the cholera toxin and immunological antigenicity of the chlamydial protein. The recombinant fusion protein (rMOMP) was expressed in E. coli, purified and analyzed by SDS-PAGE, immunoblot, and G(M1)-ELISA, and subsequently used to immunize BALB/c mice via intranasal (i.n.) and intravaginal (vag.) routes. The rMOMP protein administered via the i.n. route induced a higher concentration of anti-MOMP specific antibodies in both serum and vaginal washes as compared to mice immunized with Chlamydia or PBS. Antibody isotype analysis revealed that i.n. administration of rMOMP to mice induced higher concentrations of serum and vaginal wash IgA, IgG1, IgG2a, and IgG2b antibodies. Vaginal washes from all immunized mice following a chlamydial challenge infection were analyzed by indirect immunoflourescence to study the level of protection provided by various immunogens. Maximum protection against C. trachomatis as assessed by reduction in C. trachomatis inclusion forming units (IFU) was provided by i.n. immunization of mice with rMOMP. This is a first report using genetic fusion of cholera toxin and MOMP genes and provides a novel approach for the design and development of a mucosal vaccine against Chlamydia. (c) 2005 Elsevier Ltd. All rights reserved.