Epitope based recombinant BCG vaccine elicits specific Th1 polarized immune responses in BALB/c mice.

Aparna, J.C.; Karthika, D.; Gayatri, D.; Kannan, P.; Gupta, U.D.; Gupta, P.; Ignacimuthu, S.; Narayanan, S.

Vaccine; 2012; 30; 1364– 1370.

Abstract: Developing an efficacious vaccine is one of the highest priorities in tuberculosis research. A vaccine based on T cell epitopes representing multiple antigens is an ideal approach to generate effective cellular immunity against the disease. In the present study, we have selected four T cell epitopes from four well defined Mycobacterium tuberculosis antigens, Ag85C (Rv2903c), 10-kDa culture filtrate protein (CFP-10) (Rv3874), PPE68 (Rv3873) and INV (Rv1478). The epitope encoding genes were grafted into a Cpn 10 based epitope delivery system. The cpn 10-epitope chimeras were further cloned and expressed in BCG to obtain four rBCGs (BCG::CFP, BCG::FBP, BCG::PPE and BCG::INV). Both cellular and humoral immune responses induced by these r-BCG strains were evaluated in BALB/c mice after subcutaneous injection of a single dose of 1 × 10⁶ CFU of the individual rBCGs. Compared to the parent BCG immunized animals the splenocytes derived from rBCG vaccinated groups showed greater antigen specific proliferation, characterized with higher IFN- g response and reduced IL-4 secretion. Also rBCG vaccination was able to induce specific humoral immune response with an enhanced IgG2a/IgG1 ratio. The rBCGs therefore favor an epitope specific Th1 type response, which is known to be important for mycobacterial immunity. Further when two of the rBCGs (BCG::CFP and BCG::FBP) were tested for their protective efficacy both the rBCGs were comparable to BCG in a H37Rv challenge study performed in guinea pigs.

Keywords: Recombinant BCG; Epitope; Heat shock protein; Vaccine; Mycobacterium tuberculosis

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