The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes was at least 2,000 times more effective than the free drug in lowering the load of lung bacilli in infected animals. However, pretreatment with drug-free tuftsin-bearing liposomes did not render the pretreated animals resistant to the Mycobacterium tuberculosis infections, neither did it appreciably increase the chemotherapeutic efficacy of the liposomized rifampin. These results clearly demonstrate that liposome targeting to macrophages could considerably increase the antitubercular activity of liposomized drugs such as rifampin. Also, it shows that immunoprophylactic treatment with macrophage activators such as tuftsin does not afford any advantage in treatment of tuberculosis infections,

Summary Mycobacteria including Mycobacterium tuberculosis and Mycobacterium leprae possess multiple antigens some of which inhibit other anti-mycobacterial immune responses. Whole cell vaccines are not free from these suppressive molecules and may adversely affect the immunogenic response(s). Purified protein components having only immunogenic properties should prove to be superior vaccine(s). Mycobacterium habana, a candidate vaccine for mycobacterial infections has been dissected for analysing its antigenic myriad. A 65 kDa protein of this mycobacterium has been isolated and characterized for its protective and celJ mediated immune responses. The protein was isolated in pure form using an isotachophoresis (SDS-PAGE filtration) technique and identified with low molecular weight markers along with mAb using the immunoblot technique. Mab IIH9 has identified a 65 kDa protein in M. habana. This protein has been found to be immunoprotective in mice against M. tuberculosis H37RV infection. It generates high levels of DTH responses in mice against M. tuberculosis and M. leprae antigens and inhibits migration of sensitized cells under the antigenic influence of homologous and heterologous origin. Possibilities of developing this protein as a subunit vaccine are discussed in this report.

Lymphostimulatory and delayed-type hypersensitivity (DTH) immune responses to a candidate antileprosy vaccine Mycobacterium habana have been quantified in inbred AKR mice. M. habana vaccine in three physical states, live, heat killed and ,),-irradiated, was given intradermally to separate groups of mice and after 28 days these mice were given subcutaneous challenge with heat-killed M. leprae and heat-killed M. habana in the left hind footpad. Live BeG vaccine alone and in combination with ,),-irradiated M. habana were also compared similarly. A sufficient degree of DTH response was generated in mice by M. habana vaccine in all physical forms against two challenge antigens (lepromin and habanin). The BeG combination with M. habana did not increase the DTH response indicating internal adjuvanticity endowed in M. habana. The active hypersensitivity of immunized mice was transferable to syngeneic mice by the transfer of sensitized cells from the donor to the recipient mice intravenously. M. leprae-infected Rhesus monkey PBMe have shown comparable stimulatory response with M. habana (sonicate), and M. leprae (sonicate) antigens. The possibility of developing M. habana as a candidate antileprosy vaccine is discussed.