Epitope based recombinant BCG vaccine elicits specific Th1 polarized immune responses in BALB/c mice.
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 1×10(6)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-γ 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.
Department of Immunology, Tuberculosis Research Centre, Mayor V.R. Ramanathan Road, Chetpet, Chennai 600031, India.
Aparna Josephine
AJ
Christy
Karthika
K
Dharman
Gayatri
G
Dhandapaani
Kannan
K
Palaniyandi
Umesh D
UD
Gupta
Pushpa
P
Gupta
S
S
Ignacimuthu
Sujatha
S
Narayanan
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018274:Electroporation; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006168:Guinea Pigs; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D010957:Plasmids; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058408:Th1-Th2 Balance; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; C072681:Mycobacterium tuberculosis antigens