Immunity against Mycobacterium avium induced by DAR-901 and BCG

Abstract

The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. In this study, we tested the ability of two whole cell vaccines, DAR-901 (heat killed M. obuense) and BCG (live attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-gamma ELISPOT assay after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. Some mice vaccinated with BCG were treated with clarithromycin via gavage. Lung CFU in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Our results showed that i) DAR-901 induced cross-reactive immunity to MAC and the level of MAC cross-reactive immunity was similar to the level of immunity induced by BCG, ii) DAR-901 and BCG protect against aerosol MAC, iii) mucosal BCG vaccination provided the best protection against MAC challenge, and iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin.