CORE--ORAL RECOMBINANT SALMONELLA ANTIFERTILITY VACCINES CORE

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The ultimate goal is to construct one or more safe, efficacious, recombinant avirulent Salmonella vaccine strains, each expressing one or more sperm- or egg-specific antigens that would, upon oral immunization, induce immune responses to inhibit and/or prevent the fertilization process. In general, species of Salmonella will be attenuated by introduction of delta/cya/delta/crp mutations, and further modified to decrease survivability in blood, to be excreted in a totally avirulent nonimmunogenic form with reduced survival in nature and minimal probability for causing immunization of those not elected to be immunized. Genetic information for expression of sperm-specific and egg-specific antigens will be contained on multi-copy plasmid vectors of the balanced lethal type, wherein the asd+ gene on the vector complements a delta/asd chromosomal mutation imposing a requirement for diaminopimelic acid (DAP). Genetic information defining important sperm-specific and egg-specific antigens will be based on studies being conducted by other Center members as well as by other scientists conducting related research. The vectors with DNA inserts will be designed and constructed to enhance transcription and translation and to reduce breakdown of the protein product. We will also employ the best available methods to enhance and/or restrict the type of immune response by inclusion of sequences encoding adjuvants, immune enhancers and/or modulators and specific epitopes to enhance SIgA mucosal or IgG humoral or various cellular immune responses. The various constructs will be evaluated in a diversity of in vitro tests and the S. typhimurium and S. choleraesuis derivatives for stability and immunogenicity in mice and rabbits. Suitable S. typhi and S. paratyphi A constructs will also be made for use with primates and ultimately humans. The research will make use of modern technologies in the fields of microbiology, immunology, genetics, molecular biology and animal sciences.