Studies of resistance to experimental tuberculosis in mice vaccinated with living attenuated tubercle bacilli and challenged with virulent organisms.

Abstract

Resistance to infections with Mycobacterium tuberculosis has been studied in a number of experimental animals, but recently the suitability of mice for immunity tests has been emphasized. Stamatin and Stamatin (1) concluded that mice were less susceptible than guinea pigs. The use of mice for studies of resistance to tuberculosis was given great impetus by Dubos and associates (2a-2i) , who showed that, by controlling the size of the challenge dose of virulent bacilli injected intravenously, differences in reactions of nonvaccinated mice could be detected. Lethal infections were avoided because differences between the two groups of animals were difficult to detect. In tests to evaluate the immunogenicity of various strains of BCG, the number of organisms in selected tissues was determined because proliferation of the immunizing agent was necessary to produce protection. The degree of resistance was measured by: the comparative numbers of virulent organisms in lungs and spleens; the number of tuberculous lesions in the lungs; and the number of acid-fast organisms in each nodule of control and immunized mice. The application of these methods has been described by various writers (3-7). Crowle (8) has shown that the relative density of the lungs of vaccinated and control mice challenged with virulent tubercle bacilli may be used as an index of immunity. The survival time of control versus vaccinated mice after intravenous challenge with large numbers of virulent bacilli has also been used as a measure of resistance (9-11). Glover (12) showed that mice were susceptible to infection by aerosols of virulent bovine tubercle bacilli and that approximately 100 organisms were an infectious dose and 120,000 a lethal