A heterologous prime-boost regimen using BCG and an mRNA encoding Ag85B heightens immune response in mice

The mRNA vaccine platform holds a great promise as novel tuberculosis vaccine. In this study, the use of mRNA encoding Ag85B from M. tuberculosis (M. tb) formulated in lipid nanoparticle (LNP) was investigated as a standalone vaccine or a booster dose for BCG in mice. Two doses of Ag85 B mRNA/LNP induced robust specific humoral response and Th1 response as measured by IFN-γ-producing T cells and polyfunctional CD8⁺ T cells (IFN-γ, TNF-α, and IL-2) in spleens and lungs. A heterologous BCG prime and mRNA/LNP boost regimen induced higher response to broad M. tb antigens than one dose of BCG vaccine or homologous prime-boost regimen by mRNA/LNP. This approach produced the highest IFN-γ-producing T cells and polyfunctional CD4⁺ T cells, indicating that mRNA/LNP provided help that enhanced the response to other antigens beyond Ag85B. The mycobacterial growth inhibition assay showed that the heterologous prime boost effectively reduced mycobacterial growth to the lowest level among the groups tested in this study. Thus, by integrating the mRNA vaccine platform into the tuberculosis vaccine development, it may be possible to provide an effective strategy to control tuberculosis.