Feasibility of testing recombinant oral attenuated Salmonella vaccines in rabbits.

An effective vaccine against chancroid could take the place of therapeutic control programs, offering long-lasting protection without the risk of widespread drug resistance. Orally administered recombinant attenuated Salmonella strains are used as vaccine vectors to deliver heterologous, pathogen-derived antigens to intestinal mucosal associated lymphoid tissue, and to provide vaccine adjuvancy. Chancroid vaccines are tested in a temperature-dependent rabbit model of experimental H. ducreyi infection. However, testing of recombinant attenuated Salmonella strains as vaccine vectors has never been done in rabbits; it is usually done in mice. Anatomic and physiologic differences may limit this approach to the demonstration of vaccine feasibility in rabbits. A three-part study was designed to assess the feasibility of testing attenuated Salmonella vector vaccines in rabbits. The questions asked were, (1) what is the maximum tolerated oral dose and minimum immunogenic oral dose of attenuated Salmonella in rabbits, (2) can a recombinant antigen expressed in the attenuated vector be recognized by the rabbit immune system, and (3) will experimental H. ducreyi infection in rabbits after oral Salmonella vaccination function as a comparative quantitative virulence assay to permit vaccine evaluation? (Abstract shortened by UMI.