Enhancement of Tuberculosis Vaccine by Thymosin

DESCRIPTION (provided by applicant): Tuberculosis (TB) is a chronic infectious disease. Although most of the earths' 5.7 billion inhabitants have received the attenuated M. bovis BCG vaccine, many have still become infected and are at risk for developing clinical disease. The difficulty of compliance with lengthy and costly treatment regimens, coupled with the emergence of multi-drug resistant strains and the global AIDS crisis, have contributed to an emerging tuberculosis pandemic. An effective prophylactic vaccine is desperately needed. Most recent vaccines use non-viable bacterial proteins, lipids, or DNA; these require added adjuvants to generate a T helper 1 cellular response. We propose to evaluate the effects of thymosin, a synthetic 28 amino acid peptide with demonstrated Th1 immunomodulator properties, as an adjuvant. A well-characterized murine aerosol model of infection will be used with viable, virulent M. tuberculosis. We will evaluate the effect of thymosin on the level of antigen-specific IFNg production by circulating T cell populations; the reduction of bacterial load in lung and spleen; and conduct histopathological analyses of lung tissues to determine immune responsiveness and protective granuloma formation. Findings that indicate superior performance to BCG vaccinated controls will provide the basis for further evaluations in the more sensitive guinea pig model of infection.