Antituberculous immunity induced in mice by vaccination with killed tubercle bacilli or with a soluble bacillary extract.

It proved possible to increase the resistance of mice to tuberculous infection by vaccinating them with a suspension of avirulent tubercle bacilli killed by exposure to 2 per cent phenol. This increase in resistance was demonstrated by two different techniques: (a) observation of survival time of vaccinated animals following challenge infection with a large dose of virulent bacilli, and (b) determination of numbers of virulent bacilli in the spleens of animals 2 weeks after injection of a small infective dose. The minimum protective dose of vaccine corresponded to approximately one-tenth the acutely toxic dose. Addition of an adjuvant to the bacillary suspension markedly increased both the protective effectiveness of the vaccine and the duration of the immunity. It enhanced also the toxicity of the vaccine in approximately the same proportion. However, other lines of evidence suggested that toxicity and protective activity were independent one from the other and were the manifestations of different bacillary constituents. Extraction with absolute methanol released from the bacillary bodies a crude soluble fraction possessing low, if any, toxicity, yet capable of eliciting in mice a state of increased resistance to virulent infection. The protective activity of this methanol-soluble fraction was low; it accounted for only a small part of the total protective activity of the original material.