A novel rabies virus lipopeptide provides a better protection by improving the magnitude of DCs activation and T cell responses

•Functional CTL epitope and Th epitope of rabies virus are predicted and selected.•The position of the lipid moiety within lipopeptide constructs greatly influence on the phenotypic and functional maturation of DCs.•The branched Lipo C with two palmitic acids induces stronger specific IFN-γ producing CD8+ T cell responses.•Lipo C adjuvanted vaccine provides better protection against lethal dose of rabies virus challenge.

Besides rabies virus neutralizing antibody, non-neutralizing antibody to internal vital proteins, interferon, and possibly cell-mediated immunity also have a critical role in preventing the infection by rabies virus (RV). We identified novel CTL and Th epitopes which could induce lymphocyte proliferation and IFN-γ, IL-4 production, and designed linear and branched lipopeptides with these selected CTL and Th epitopes. Compared to linear construct, branched lipopeptides, especially Lipo C, stimulate stronger phenotypic and functional maturation of DCs, as well as more efficient CD8+ T cell responses, evaluating by using FACS, G333–341 tetramer staining and specific CTL assay. Lipo C could also assist rabies vaccine to induce an instant rabies virus neutralizing antibody production, and better protection against rabies virus challenge at early stage. These data reveal that Lipo C could be a promising component for developing novel rabies vaccines.