Immunity Against Mycobacterium avium Induced by DAR-901 and BCG

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Increasing prevalence of pulmonary nontuberculous mycobacteria (NTM), primarily Mycobacterium avium complex (MAC), in Europe and North America.
• Suboptimal treatment outcomes for pulmonary MAC, with 30-40% failure rates, highlighting the need for novel vaccines.

Purpose of the Study:

• To evaluate the efficacy of two whole-cell vaccines, DAR-901 and BCG, in inducing cross-reactive immunity against MAC.
• To assess the protective capabilities of these vaccines against aerosolized MAC infection in a mouse model.
• To investigate the safety profile of a modified BCG vaccine (tetR BCG) for mucosal administration.

Main Methods:

• Immunization of BALB/c mice with DAR-901 or BCG (intradermal, subcutaneous, or intranasal).
• IFN-γ ELISPOT assays to measure cross-reactive immunity.
• Aerosol challenge with MAC, followed by quantification of lung colony-forming units (CFU), histopathology, and flow cytometry analysis.
• Evaluation of tetR BCG in cystic fibrosis-prone mice and assessment of doxycycline's effect on BCG CFU.

Main Results:

• Both DAR-901 and BCG induced significant MAC cross-reactive immunity and protected against aerosol MAC challenge.
• Mucosal BCG vaccination demonstrated superior protection compared to systemic BCG and DAR-901.
• BCG vaccination did not impede clarithromycin efficacy, and tetR BCG with doxycycline treatment reduced lung BCG CFU without compromising MAC immunity.

Conclusions:

• DAR-901 and BCG vaccinations are effective in generating MAC cross-reactive immunity and protecting against MAC infection.
• Intranasal BCG vaccination provides the most robust protection against pulmonary MAC challenge.
• TetR BCG represents a potentially safer alternative for mucosal BCG vaccination strategies.