Prospects for low dose BCG vaccination against tuberculosis

Efficacious vaccination against fast growing pathogens results in a rapid, secondary immune response on natural infection; this provides protection to the vaccinated individual in the race between developing effective immunity and the rapid multiplication of the pathogen. In certain chronic diseases, due to slow growing pathogens, cell-mediated immunity alone can contain the infection, and yet an antibody response is sometimes induced, at the expense of the cell-mediated response, upon natural infection. Such situations arise in leprosy and the leishmaniases and most probably in tuberculosis. AIDS and syphilis. In these cases, the purpose of vaccination must be to ensure that a stable, protective, cell-mediated immune response is inevitably induced upon natural infection. We believe we have developed a general strategy for causing a pathogen-specific imprint upon the immune system so that a stable, protective, cell-mediated response is inevitably induced in all individuals upon natural infection. BALB/c mice are "susceptible" to Leishmania major in the sense that they mount a non-protective antibody response on substantial infection, and consequently suffer chronic and progressive disease. We have demonstrated that infection with low doses of parasites induces only cellular immunity, and establishes the desired imprint. Mice exposed to low doses and challenged some months later with a substantial, normally pathogenic dose of parasites, mount a stable, protective, cell-mediated response and the vaccinated "susceptible" mice withstand the infection. We have recently managed to achieve a similar lock of the immune response of BALB/c mice to BCG into a cell-mediated mode by low-dose exposure.(ABSTRACT TRUNCATED AT 250 WORDS)