The efficacy of live tuberculosis vaccines after presensitization with Mycobacterium avium

Abstract

The variable efficacy of BCG in humans has been extensively documented but its cause is still not well understood. One possible reason for this variation is the effect of presensitization with environmental mycobacteria. To investigate in guinea pigs the effects of presensitization with well characterized Mycobacterium avium strains on the vaccine efficacy of BCG and of two recently developed, avirulent strains of Mycobacterium bovis. Two strains of M. avium containing the DNA insertion element IS901 (M. avium+) and two strains not containing this element (M. avium-) were inoculated subcutaneously or by oral administration into guinea pigs to assess their virulence in these animals and their ability to induce delayed type hypersensitivity to tuberculins. Subsequently, groups of guinea pigs presensitized with orally administered M. avium+ and M. avium- and a control group were vaccinated with BCG, or one of two newly attenuated strains of M. bovis. All groups were then challenged by the aerosol route with virulent M. bovis. Vaccine efficacy was assessed 5 weeks later by the presence of macroscopic lesions and bacterial counts of spleen and lung. No macroscopic lesions were observed in any of the guinea pigs inoculated with strains of M. avium+ or M. avium- and all animals gave delayed-type hypersensitivity skin-test reactions to avian PPD. In the vaccine experiment, presensitization with orally administered M. avium+ alone produced a low level of protection against subsequent challenge with virulent M. bovis. In the absence of presensitization with M. avium or after presensitization with an M. avium- strain, BCG and two attenuated strains of M. bovis produced significant levels of protection. No additional protection was observed in lungs of guinea pigs presensitized with M. avium+ and subsequently vaccinated with BCG. In contrast, both newly attenuated strains of M. bovis induced significant protection in lungs after such presensitization. Presensitization of guinea pigs by the oral administration of M. avium+ provides a model for testing vaccines under conditions where the efficacy of BCG has been compromised by prior sensitization with environmental mycobacteria.