The objective of this proposal is to develop a recombinant polytypic vaccine for Chlamydia trachomatis infections. C. trachomatis is one of the most common sexually transmitted pathogens in the Western world and in underdeveloped countries is the etiological agent of trachoma and lymphogranuloma venereum a sever systemic disease. Therefore, an effective vaccine is needed to limit the morbidity and mortality associate with this organism. In this proposal the first step is toe construct a chimeric vaccinia virus vaccine with the gene coding for the major outer membrane protein (MOMP) of the C. trachomatis L3 serovar. Antibodies to this protein have been shown to occur in a majority of Chlamydial infections and furthermore, polyclonal and monoclonal antibodies to the MOMP are known to neutralize Chlamydial infectivity. The MOMP gene will be inserted into a vaccinia virus and the recombinant virus will be tested for expression of MOMP. Mice will be inoculated with the chimeric vaccinia virus-C. trachomatis L3 MOMP vaccine and then they will e challenged with infectious Chlamydiae. The ability of the vaccine to prevent or to modify systemic homotypic and heterotypic Chlamydial infections will be tested. In the case that the C. trachomatis L3 MOMP vaccinia vaccine protects against a challenge with all the C. trachomatis serovars we will subclone the four antigenic variable sequences (VS1, VS2, VS3, and VS4) of the C. trachomatis L3 MOMP into the vaccinia virus and we will test them for their ability to provide protection against a challenge with the 15 C. trachomatis serovars. If on the other hand the C. trachomatis L3 MOMP vaccine proves to have only homotypic or subspecies specificity we will then proceed to isolate and characterize the MOMP genes from the J, E and F serovars and to construct vaccinia virus C. trachomatis chimeras. Thee chimeric vaccines, independently and in combination, will be tested for their ability to protect against infectious homotypic and heterotypic C. trachomatis challenges. We expect that vaccination with the genes from the four serovars will protect the mice against a challenge by any of the 15 C. trachomatis serovars. If this proves to be true, a single vaccinia virus-C. trachomatis chimera vaccine will be constructed which expresses the C. trachomatis MOMP genes from the L3, J, E and F serovars. In the case that we obtain protection with this combined vaccine, and based on the data obtained with the L3 vaccine, we will construct a chimeric vaccinia virus polytypic C. trachomatis vaccine with those variable sequences of the L3, J, E and F serovars that confer protection. This recombinant vaccinia virus-C. trachomatis vaccine will be tested for its ability to protect mice against a systemic challenge with all the C. trachomatis serovars.
Showing the most recent 10 out of 11 publications
