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

Christy, A J and Dharman, K and Dhandapaani, G and Palaniyandi, Kannan and Gupta, U D and Gupta, P and Ignacimuthu, S and Narayanan, Sujatha (2012) Epitope based recombinant BCG vaccine elicits specific Th1 polarized immune responses in BALB/c mice. Vaccine, 30 (7). pp. 1364-1370. ISSN 0264-410X

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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-� 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.

Affiliation:	ICMR-National Institute for Research in Tuberculosis
Item Type:	Article
URI:	http://eprints.nirt.res.in/id/eprint/1141

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