Immunogenicity and safety of Mycobacterium tuberculosis culture filtrate proteins in non-human primates

The development of improved vaccines is considered a high priority in the e ffort to control tuberculosis (TB) world wide. Results from several studies performed in relevant animal models have demonstrated that Mycobacterium t uberculosis secreted antigens may represent major components of improved TB vaccines. To characterize further the M. tuberculosis secreted antigens as they relate to specific features important for vaccine development, rhesus macaques were immunized with either one of two different preparations cont aining M. tuberculosis culture filtrate (CF) proteins. These preparations d iffered in relative protein content and in the presence or absence of lipoa rabinomannan. Animals received a total of three monthly intramuscular injec tions consisting of CF proteins resuspended in RIBI adjuvant and were teste d for development of specific antibody and cellular proliferative responses . In addition, all animals were constantly monitored for local and systemic reactions as well as for the development of DTH reactions to intradermal t uberculin injection. Results from this study show that the two CF preparati ons are relatively safe and immunogenic in non-human primates. These two CF preparations differed in their ability to induce specific antibody respons es, but were comparable in their ability to induce specific cellular prolif erative responses. Induction of both humoral and cellular responses occurre d even in presence of pre-existing antibodies directed against M. tuberculo sis antigens. However, these responses appeared to be short-lived. Only one of the four animals produced interferon-gamma (IFN-gamma) in response to i mmunization with CF proteins. No DTH reaction to intradermal tuberculin inj ection was observed in any immunized animal. Although it is clear that addi tional studies are required to design strategies for the improvement of the immunogenicity of CF proteins, our observations support the currently acce pted view that secreted protein-based preparations may represent promising vaccine candidates for TB.