The goal of this investigation is to develop the invasin gene as a vaccine against M. tuberculosis infection in the human host. Up to the present time, the only known and generally accepted vaccine-BCG-is a living attenuated one, which has shown variable efficacy in the countries where it has been used. Although efforts by other investigators in the direction of obtaining non-viable vaccine have not proved successful, the concept of a new candidate vaccine certainly merits a high priority. The cloned invasin, in combination with selected adjuvants will be evaluated for protection against TB infection and disease in a mouse model. The designed proposal will investigate the immunoprotective potential of the invasin gene. The investigators propose to: i) immunize mice using the invasin protein; ii) characterize the immune responses of humans with tuberculosis to the invasin protein; and iii) produce monoclonal antibodies and mouse T cell lines and clones specific to the invasin protein. Parts i and ii will be addressed in the first six months of the grant period. Part iii will be considered in subsequent years.
The commercial potential of such a vaccine would be significant, if the non-living vaccine shows a high degree of promise as an immunotherapeutic and possibly immunoprophylactic agent.
