A novel DNA vaccine against Mycobacterium tuberculosis infection (VAC4P.1109)

Abstract

Abstract Background: Mycobacterium tuberculosis (M.tb.) pandemic continues to grow together with serious issues of increasing drug resistance, HIV co-infection and mortality. Since the existing BCG vaccine does not provide significant protection in adults, novel protective strategies should be explored with urgency. Methods: DNA vaccines that express TB antigens Ag85B, ESAT-6, Rv2660c and fusion BER, were investigated in BALB/c mice intramuscularly with electroporation (EP). Immunogenicity and efficacy assessments of these DNA vaccines were then determined before or after aerosol challenge of 100CFU M.tb H37Rv strain. Results: Compared with BCG and other DNA/EP vaccines, pBER/EP induced high frequency of Ag85B-specific CD8+ T cells (up to 41%) in tetramer assay. Moreover, pBER/EP also elicited significantly higher frequencies of antigen-specific CD4+ T cells by ELIspot and ICS assays. Surprisingly, these T cell responses were also significantly higher than those induced by a heterologous DNA/EP prime and vaccinia-85B boost regimen. Critically, pBER/EP conferred significantly better protection against M.tb H37Rv challenge when compared to other DNA/EP vaccines, with lower CFU count in the lungs (p<0.01) and the absence of lung pathology. Conclusions: pBER/EP is a promising DNA vaccine candidate that does not have major issues of safety and pre-existing anti-vector immunity (e.g. vaccinia vector). Our findings warrant further investigation of pBER/EP for TB prevention and immunotherapy.