MUCOSAL IMMUNE RESPONSES OF A RECOMBINANT CHLAMYDIA TRACHOMATIS MOMP PROTEIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases in the world. We have developed a prototype mucosal vaccine utilizing the recombinant C. trachomatis mouse pneumonitis MOMP (major outer surface protein) subunit protein. In this prototype the MOMP molecule is genetically fused with modified cholera toxin (CTB) as a mucosal adjuvant (rMOMP-CTB). We have reported that mice immunized intranasally with this vaccine develop strong mucosal and systemic immune responses. In addition, mucosal immunization with rMOMP-CTB protected mice from a challenge infection with live C. trachomatis. We next investigated the role that cytokines may play in protecting mice from this challenge infection. Spleen cells obtained from immunized mice were restimulated in vitro with rMOMP, and supernatants were collected after 48 hr post-stimulation. Th1 (IL-2, IL-12p40 and IFN-y) and Th2 (IL-4, IL-5 and IL-10) cytokines in supernatants were analyzed using cytokine ELISA's. Mice immunized with rMOMP elicited Th1 (IFN-y and IL-12p40) and Th2 (IL-5) type responses. The levels of both IFN-y and IL-12p40 cytokines were comparable to those that were induced by cells from C. trachomatis immunized mice. However, cells from the C. trachomatis mice produced more IL-10 than those from rMOMP immunized mice. Interestingly only cells from rMOMP mice induced high levels of IL-5. This finding is of significance, and correlates with the high systemic and mucosal production of IgA in these mice before and after a challenge infection with live C trachomatis. Murine IL-5 is known to stimulate the production of IgA by stimulated B cells. Moreover, this cytokine is crucial for B-cell isotype switch, growth and differentiation into IgA-secreting plasma cells. These findings strongly suggest that rMOMP elicited strong Th1/Th2 cytokine responses that correlated with protective immunity in rMOMP immunized mice than in the C. trachomatis mice.