Fusion of HBsAg and prime/boosting augment Th1 and CTL responses to HCV polytope DNA vaccine

Abstract

Correlation of hepatitis C virus (HCV) spontaneous resolution with Th1 and CD8(+)CTL responses during natural infection implies the potentiality of poly-CTL-epitopic HCV vaccines. We recently reported in silico design and construction of DNA vaccines (pcPOL-plasmids) harboring HCV CTL epitopes. Herein, we provide data of mice immunization by pcPOL, (encoding; core(132-142) [C], E2(405-414) [E(4)], E2(614-622) [E(6)] and NS3(1406-1415) [N] CD8(+)CTL epitopes as CE(4)E(6)N polytope) and its HBsAg-fused counterpart (pcHPOL), compared to the adjuvant-formulated (Montanide+CpG) CE(4)E(6)N synthetic-peptide immunization. All vaccinated groups developed different levels of cellular responses, however, only the pcHPOL-immunized mice elicited strong CTLs and IFN-gamma-secreting cells that were further augmented towards a Th1 response and partial tumor protection by DNA-prime/peptide-boosting regimen. Priming with HBsAg alone could not afford its augmenting effect indicating the importance of priming by polytope itself. Hence, fusion of immunocarriers like HBsAg conjoined with DNA-prime/peptide-boost immunization regimen seems a strategy to enhance the epitope-specific immune responses towards poly-CTL-epitopic vaccines.