Comparison of the immunogenicity of vaccines prepared from viable Mycobacterium bovis BCG, heat-killed Mycobacterium leprae, and a mixture of the two for normal and M. leprae-tolerant mice

Intradermal vaccines consisting of viable Mycobacterium bovis BCG, heat-killed Mycobacterium leprae, or mixtures of the two were titrated in mice in doses of 10(5.2), 10(5.8), 10(6.4), 10(7.0), and 10(7.6) acid-fast bacilli. The immune response was measured by sensitization (48 to 72 h foot pad enlargement on challenge with 10(7.0) heat-killed M. leprae) and by protection against infection with a viable M. leprae challenge. There was increasing response with increasing dose of vaccine, and overall the responses to the three vaccines were similar. At the lowest dose, however, the combination of BCG and M. leprae gave superior protection. The local reaction to the vaccines in the lower dose range was less severe with the M. leprae vaccine. In another experiment, the three vaccines were compared in normal mice and in mice that had been rendered tolerant by intravenous injection of M. leprae. The tolerant mice developed no measurable sensitization on vaccination with M. leprae, but they developed partial but distinct sensitization on vaccination with BCG, alone or in combination with M. leprae. The tolerant mice developed little or no protection with any of the vaccines, however..

Kinetic testing of drugs against Mycobacterium leprae in mice. Activity of cephaloridine, rifampin, streptovaricin, vadrine, and viomycin

A series of drugs that had been found active against Mycobacterium leprae in mice by the continous method of drug administration was tested by the kinetic method. Vadrine and vyomivin were found inactive. Cephaloridine, streptovaricin, and rifampin gave bactericidal-type results. In a second experiment, rifampin was found to have distinct bactericidal effect when given for only 2 days. The plasma levels of rifampin that were associated with bactericidal effect in mice were in the range reported for man receiving acceptable dosages of rifampin. Cephaloridine and, especially, rifampin merit further investigation in clinical trials in leprosy patients, either as single drugs or in combination with other active drugs. The combination of rifampin and dapsone (DDS) or acedapsone (DADDS) appear to provide the advantages of tboth drugs.