The overall aim of our studies is to derive a potential HCV vaccine, based on the induction of HCV-specific CTL. To do so, we propose in the present Phase I study, to identify a synthetic formulation composed of at least two A2-restricted CTL epitopes derived from conserved regions of the HCV genome. Such formulation will also contain universal T helper epitopes and will be demonstrated to be efficacious in inducing specific A2-restricted CTL responses in vivo, utilizing HLA A2/Kb transgenic mice. In parallel studies additional potential epitopes specific for several of the major HLA types will also be identified.
The proposed research has two main specific applications relating to hepatitis C infection. l) Development of an original type of prophylactic vaccine specifically targeting HCV sequences that are highly conserved and/or derived from internal viral proteins, and 2) A therapeutic vaccine for chronic hepatitis C infection. This technology has wide applicability to other chronic viral diseases and cancer.
Oseroff, C; Sette, A; Wentworth, P et al. (1998) Pools of lipidated HTL-CTL constructs prime for multiple HBV and HCV CTL epitope responses. Vaccine 16:823-33 |