Subunit vaccine candidate with adjuvant confers protection against clinical Mycobacterium avium in wild type and immunocompromised mouse models

Abstract

Abstract Nontuberculous mycobacteria (NTM) are a group of 170 species of mycobacteria that are steadily increasing in incidence and prevalence. NTM cause a significant amount of morbidity and mortality and overtake Mycobacterium tuberculosis in prevalence in certain regions of the world, including the United States. M. avium, a clinically significant NTM, is known to cause a tuberculosis-like pulmonary disease that is often difficult to treat. Due to this quietly emerging health threat, we evaluated the ability of a subunit vaccine (ID91) with the Toll-like receptor agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water stable nano-emulsion (GLA-SE) to confer protection in both the C57BL/6 (wild type) and Beige (immunocompromised) mouse models. We first established a challenge model with a low dose aerosol of the virulent clinical isolate M. avium 2–151 smt and monitored bacterial burden and immune responses to infection over time. Next, cohorts of mice immunized prophylactically with ID91+GLA-SE or bacillus Calmette–Guérin (BCG) were subsequently challenged with M. avium 2–151 smt. Not surprisingly, the immunocompromised Beige mice sustained a larger bacterial burden in the lungs and spleen compared to C57BL/6 mice regardless of treatment. However, both ID91+GLA-SE and BCG significantly reduced pulmonary bacterial burden in both models. Variable innate and adaptive pulmonary immune response kinetics in C57BL/6 and Beige mice in response to M. avium 2–151 smt infection were observed. This work demonstrates the first proof-of-concept study that a subunit vaccine candidate (ID91+GLA-SE) confers prophylactic protection against NTM and suggests further vaccine development may help reduce the burden of disease.