Vaccination against tuberculosis with nonliving vaccines. I. The problem and its historical background.

Abstract

shown to influence the immunizing capacity of the product. Swedberg concluded that heatkilled human tubercle bacilli in big doses and Sadelkow (1951) postulated that the relative dispersed in paraffin oil reveal the same unquesresistance of children to tuberculosis stemmed tionable immunizing effect as living BCG. from their continuous ingestion of tubercle bacilli The subcutaneous route of vaccination with weakened (abgeschwacht) by sunlight (201). killed vaccines was found to be a satisfactory He vaccinated 2 (1) guinea pigs with ultravioletone, and the high protective activity of killed irradiated bacilli and six weeks later fed them vaccines was seen even when the animals were dandelion leaves dipped in a culture of living viruchallenged by the intravenous route. lent tubercle bacilli. The animals apparently Yanagisawa, Kanai, Shiga, and Ito (1951) remained well. protected guinea pigs by vaccination with 0.1 Purified tuberculoprotein and -polysaccharide mg. of heat-killed BCG suspended in paraffin, or preparations were reported by Seibert (1950) to with 0.1 ml. of a paraffin extract of killed BCG, be devoid of immunogenic activity (202). to the same extent against subsequent tuberIn a study of the effects of cortisone on tuberculous infection as was possible with living BCG culosis in mice, Solotorovsky, Gregory, and (205). The degree of protection in their experiStoerk (1951) also investigated the effect of the ments was evaluated by comparing the extent steroid on animals vaccinated prior to infection of systemic tuberculous disease of the vaccinated with steam-killed human tubercle bacilli (203). and control animals sacrificed at intervals after Each animal received six intraperitoneal injecinfection. Yanagisawa and Kanai (1952) also tions of 0.5 ml. each of the steamed culture and claimed a protective effect for a tuberculin prepwas challenged intravenously two days after the aration administered intramuscularly in oil (206), last injection. The vaccinated animals survived but the reported tuberculin-sensitizing properties longer than the unvaccinated controls if they of this preparation suggest that it may have been were not subjected to cortisone; cortisone overcontaminated with intact bacillary bodies. Kanai came the vaccination-induced protection. and his co-workers (1952) vaccinated school A comprehensive investigation of antitubercuchildren in Japan with heat-killed tubercle bacilli losis vaccines killed by a variety of methodssuspended in peanut or paraffin oil by the scariheat, ultraviolet irradiation, urea, and extreme fication method (207); local ulcerations did not pH-was reported in 1951 by Swedberg (204). develop. Mice and guinea pigs were employed, and in Birkhaug and Darricarrere (1952) reinvesmost of the experiments survival time after tigated the ultraviolet-killed vaccines prepared infection was used to measure the degree of by Sarber's (see200) and Milzer's (see199) groups resistance. Large numbers of animals were used, (208). The preparations employed by Birkhaug and the results were subjected to statistical and Darricarrere were three to fifteen months analysis. It was again found that killed vaccines old at the time of testing. Groups of 18 to 24 prepared from different strains of tubercle guinea pigs were given three intraperitoneal bacilli differed in their immunogenic activity, injections of 5 mg. each, and were challenged one heat-killed BCG proving inferior to heat-killed to three months later by the intramuscular route. human tubercle bacilli. The pH of the suspension Three-and-a-half months after infection, the in which tubercle bacilli were killed by heat was survivors were killed, and the extent of tubercu-