The present communication deals with the various important issues about the BCG vaccine being using for the control of tuberculosis. The first issue is of BCG vaccine. BCG daughter strains, namely, French, Glaxo, Japanese and many others, inspite of minor differences evoke similar immune responses and none of the strains is superior to other.

BCG Vaccine↗

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BCG-induced mucosal immune responses.

The induction of mucosal immune responses is particularly important for protection against diseases for which entry and pathogenesis are clearly related to the mucosal system, such as salmonellosis, AIDS or tuberculosis. We investigated the immune responses in guinea-pigs vaccinated by BCG via the respiratory compared to the intradermal route. The results demonstrate that the aerogenic BCG induced a better activation of broncho-alveolar macrophages and a substantially improved protective effect against a virulent challenge with Mycobacterium tuberculosis. We also used a DNA recombinant BCG expressing LacZ gene to investigate the influence of various routes of administration on the immunogenicity of the beta-galactosidase, a foreign antigen expressed by the LacZ-BCG recombinant. Thus, lymph-node proliferative responses, delayed type hypersensitivity and antibody responses specific for beta-galactosidase can be produced in guinea-pigs immunized orally, respiratorily and intradermally. The respiratory and especially the oral route of administration produced higher mucosal and systemic immune responses compared with the intradermal route of immunization. Moreover, the oral immunization of mice with recombinant BCG induced IgA responses which can be detected both in sera and in intestinal secretions. In conclusion, BCG recombinants may be of potential use as an adjuvant vaccine.

Animals↗

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Viability, heat stability and immunogenicity of four BCG vaccines prepared from four different BCG strains.

Four BCG strains, French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077, among those most widely used throughout the world for tuberculosis vaccination, were prepared according to the respective conditions in each BCG-production unit. These 16 vaccine preparations were distributed and compared using standardized in vitro and in vivo conditions, based on optical density and bacillary mass/ml. The results presented in this report concern only the 4 freeze-dried BCG strains prepared by the Institut Pasteur BCG unit. It is shown that these 4 preparations differ in their in vitro characteristics such as growth, morphology, heat stability and viability, tested by colony-forming units and the ATP content. In addition, statistically significant differences were observed in biological control tests performed in guinea-pigs and mice when they were immunized with the same concentrations of 4 reconstituted vaccines. For instance, in tests measuring hallmarks of cell-mediated immunity--such as local granuloma formation, spleen index, delayed-type hypersensitivity to tuberculin, and non-specific immunopotentiation to unrelated antigen--a ranking order of relative immunopotency of the four strains was made, giving the following classification in decreasing order: French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077. Specific acquired resistance after BCG vaccination in mice was obtained with all four vaccines. However, higher protection was observed in mice vaccinated with Glaxo-1077 and French 1173-P2 strains. No obvious correlation existed between the intensity of cellular post-vaccination resistance and the above CMI tests, except those concerning the three-week index of BCG infection measured in the spleen, which correlated with the protection test.

Adenosine Triphosphate↗

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BCG-induced anaemia in mice: no direct effect of the growth of bacilli.

Mice receiving viable BCG intravenously (i. v.) rapidly and transiently develop anaemia, the origin of which is a decrease in erythropoietic progenitor cells. BCG-induced anaemia appears to be related to conditions which allow the development of a protective immune response against BCG infection. An increased number of blood phagocytes is strictly associated with the development of the anaemia and is dependent on the presence of T lymphocytes. Anaemia does not occur in some strains of mice: C3H/He Past strain was chosen as a typical non-responding strain and the opposite C57BL/6 strain as a responding one. Enumerations of BCG particles were performed in haemopoietic tissues, spleen and bone marrow of mice of the two strains in order to appreciate an eventual direct effect of bacilli growth on erythropoiesis. We never observed the particular growth of bacilli in mice which developed anaemia. On the contrary, the number of BCG viable units decreased progressively in responding strain C57BL/6 when numerations were performed after the 2nd month of the infection. This ability of C57BL/6 mice to control the infection contrasted with a relapse of bacilli growth in C3H.

Anemia↗