Use of conventional or replicating nucleic acid-based vaccines and recombinant Semliki Forest virus-derived particles for the induction of immune responses against hepatitis C virus core and E2 antigens

Replicating and nonreplicating nucleic acid-based vaccines as well as Semli ki Forest-recombinant Viruses (rSFVs) were evaluated for the development of a vaccine against hepatitis C virus (HCV). Replicating SFV-DNA vaccines (p SFV) and rSFVs expressing HCV core or E2 antigens were compared with classi cal CMV-driven plasmids (pCMV) in single or bimodal vaccine protocols, in v itro experiments indicated that all vaccine vectors produced the HCV antige ns but to different levels depending on the antigen expressed. Both replica ting and nonreplicating core-expressing plasmids induced, upon injection in mice, specific comparable CTL responses ranging from 10 to 50% lysis (E:T ratio 100:1). Comparison of different injection modes (intramuscular versus intraepidermal) and the use of descalating doses of DNA (1-100 mug) did no t show an increased efficacy of the core-SFV plasmid compared with the CMV- driven one. Surprisingly, rSFVs yielded either no detectable anticore CTL o r very low anti-E2 antibody titers following either single or bimodal admin istration together with CMV-expressing counterparts. Prime-boost experiment s revealed, in all cases, the superiority of DNA-based only vaccines. The a nti-E2 antibody response was evaluated using three different assays which i ndicated that all generated anti-E2 antibodies were targeted at similar det erminants. This study emphasizes the potential of DNA-based vaccines for in duction of anti-HCV immune responses and reveals an unexpected and limited benefit of SFV-based vaccinal approaches in the case of HCV core and E2. (C ) 2000 Academic Press.