ABSTRACT
Background: considering the immunosuppressive effects and prevalent mutations in some HCV antigens, induction of CD8[+] T cell responses is focused on conserved and critical epitopes which as a multi-epitope vaccine can prevent the chronic nature of the disease
Materials and Methods: two immunodominant HLA-A2-restricted human epitopes [E2[614- 622] and NS3[1406-1415]] and two H-2[d]-restricted mouse epitopes [core[132-142] and E2[405-414]] were designed in a sequential tandem, predicted by immunoinformatic analyses. Following the synthesis, related nucleotide sequence was cloned into the pcDNA3.1 vector with and without the fusion of hepatitis B surface antigen [HBsAg]. Two constructed plasmids [pcDNA3.1.HPOL and pcDNA3.1.POL, respectively] were evaluated for the protein expression and secretion in Cos-7 cell line. After the vaccination of BALB/c mice [n=6 in each group] with different DNA and peptide immunization regimens, CD8[+] T cell activity as well as the type and protective potency of the induced responses were evaluated
Results: despite the induction of epitope-specific responses in pcDNA3.1.POL injected mice, the group immunized with pcDNA3.1.HPOL indicated a significant increase in the number and activity of CD8[+] T cells [P<0.05]. Peptide boosting of this group [formulated in two human-compatible adjuvant] still led to the more activation of CD8[+] cells, induction of Th1 response and the inhibition of tumor model growth [P<0.05]
Conclusion: fusion of HBsAg as a particle-forming sequence and the source of helper epitopes along the DNA-prime/peptide-boosting immunization regimen are proposed as two promising strategies to improve the CTL multi-epitope vaccines against HCV