Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.We evaluated IFN-γ responses by ELISpot and antibody responses by enzyme linked immunosorbent assay in C57BL/6 and BALB/c mice after three doses of DAR-901. In an aerosol challenge model, we evaluated the protective efficacy of the DAR-901 booster in C57BL/6 mice primed with BCG and boosted with two doses of DAR-901 at 4 dosage levels in comparison with homologous BCG boost. lysate or purified protein derivative. Among animals primed with BCG, boosting with DAR-901 at 1 mg provided greater protection against aerosol challenge than a homologous BCG boost (lungs P = 0.036, spleen P = 0.028). compared to a homologous BCG boost