Preliminary observations on experimental leprosy in tupaias (Tupaia belangeri yunalis).

The Tupaia belangeri yunalis (tree shrew) is one of the primitive primates. They were inoculated subcutaneously in the footpad or intravenously with Mycobacterium leprae from a patient with multibacillary leprosy. As controls, the footpads of CFW mice were inoculated with the same suspension of M. leprae. The results showed growth of acid-fast bacilli (AFB) in the footpads of locally inoculated CFW mice and in the footpads of both locally and intravenously inoculated tupaias. Whereas the numbers of AFB declined in the footpads of CFW mice after 12 months, they increased in the tupaia footpads, up to 2.44 x 19(9) AFB/g of tissue. The footpads of one tupaia were swollen, which on section revealed a granulomatous infiltration, including foamy and heavily infected macrophages. M. leprae were also seen in the branches of cutaneous nerves. Also AFB occurred in some viscera. Preliminary studies indicate that the AFB multiplying in tupaias are M. leprae.

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.

Sensitization or tolerance to Mycobacterium leprae antigen by route of injection.

Aqueous suspensions of heat-killed Mycobacterium leprae in a dose of 10(7) organisms were highly immunogenic when injected intradermally (i.d.). The same dose of bacteria did not sensitize when given intraperitoneally (i.p.) or intravenously (i.v.), and did so only minimally at best when given subcutaneously. The i.d. route was the most immunogenic for sheep erythrocytes also. M. leprae injected i.p. or i.v. stimulated immune tolerance to M. leprae challenge i.d. In older mice (greater than or equal to 8 weeks), the i.v. injections gave more complete tolerance. Mice that had been rendered tolerant by i.v. injections maintained their tolerance for at least 168 days. Prior UV irradiation of intact mice prevented sensitization by the i.d. route. In normal mice, living M. bovis BCG given i.d. produced good sensitization to M. leprae. Mice that had been made tolerant by i.v. injection of M. leprae could be partially sensitized to M. leprae by i.d. immunization with BCG; mixtures of living BCG and heat-killed M. leprae were no more effective than BCG alone. These findings appear to have relevance to the pathogenesis of lepromatous leprosy and its immunoprophylaxis.