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Clin. Vaccine Immunol. doi:10.1128/CVI.00274-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Targeted Multi-Subunit Vaccination Approach to Evaluate Cross-Serovar Protection against Genital Chlamydial Infection

South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249; Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229

^* To whom correspondence should be addressed. Email: Bernard.arulanandam{at}utsa.edu.

	Abstract

An important consideration for anti-chlamydial vaccine development is the induction of cross-serovar protection, since multiple serovars (D-L) of Chlamydia trachomatis cause genital infections. We have shown previously that vaccination with C. trachomatis-derived recombinant chlamydial protease-like activity factor (rCPAF) induced significant earlier resolution of C. muridarum infection and reduced oviduct pathology. However, the vaccinated mice continued to shed chlamydiae for up to two weeks after challenge. In this study, recombinant C. trachomatis serovar D proteins-major outer membrane protein (rMOMP), inclusion membrane protein A (rIncA), and rCPAF were administered intranasally, individually or in combinations, with murine interleukin-12 (IL-12) as adjuvant, and cross-species immunity against intravaginal C. muridarum infection was examined. rCPAF+IL-12 immunization, compared to rIncA+IL-12 or rMOMP+IL-12, induced the greatest antigen-specific IFN- production from purified CD4⁺ T cells and concurrently enhanced serum antibody production. All (100%) the animals vaccinated with rCPAF+IL-12 alone, or in any combination, completely resolved the infection by day 18 after challenge, compared to animals vaccinated with rIncA+IL-12 (50%), rMOMP+IL-12 (33%) or PBS (mock; 0%). Moreover, oviduct pathology in mice vaccinated with any regimen that included rCPAF, but not rMOMP+IL-12 or rIncA+IL-12 alone, was markedly reduced when compared to mock-immunized animals. The addition of rMOMP and/or rIncA did not significantly enhance the rCPAF+IL-12-induced effect on bacterial clearance or oviduct pathology. These results suggest a greater conservation of protective linear antigenic epitopes within CPAF than MOMP or IncA, across the examined serovars, and the need to identify other highly conserved antigens for use with rCPAF in a multi-subunit recombinant vaccine.