Efficacy of a prime/boost regimen including BCG and recombinant protein in an HN878 challenge of C57BL/6 mice (P4296)

Abstract

Abstract Tuberculosis remains a major concern despite the widespread use of BCG vaccine. Since BCG-induced protection against adult pulmonary TB has been highly variable, vaccines that confer better, more complete protection are needed and recombinant proteins in the presence of adjuvant are currently being evaluated in this context. C57BL/6 mice were used in an immunogenicity and aerosol challenge study to evaluate the efficacy of a heterologous prime-boost vaccination regimen. Adult females aged 6-8 weeks old were vaccinated with either BCG SSI alone, or in conjunction with a recombinant fusion protein expressing Ag85B, Ag85A and Rv3407 with a poly(I:C)-based TLR3 adjuvant. Prior to challenge, a subset of mice were used to evaluate immune responses by IFN-γ ELISA and flow cytometry. This combination elicited a strong Th1 response as evidenced by high levels of IFN-γ, IL-2 and TNF expression in CD4+ T-cells from splenocytes. Mice were challenged with 50-100 CFU of aerosolized M.tuberculosis strain HN878. Spleens and lungs were used to determine viable bacterial load (CFU) and lungs fixed for routine histopathology. We observed a statistically significant reduction in lung CFU at 12 weeks post infection in the prime-boost vaccine group compared to BCG alone. The use of a recombinant protein plus adjuvant as a boost to the widely used BCG SSI vaccine was shown to be immunogenic and to elicit an increased level of protection over BCG alone in the lungs of adult C57BL/6 mice.