Protection and immunological study on two tetraspanin-derived vaccine candidates against schistosomiasis japonicum

: Tetraspanins (TSPs) are proteins found on the surface of helminth parasites of the genus Schistosoma and are regarded as potentially protective antigens. The large extracellular loop of Schistosoma mansoni tetraspanin-2, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. It is well recognized that CD4(+) T-cell-dependent immunity might play an important role against schistosomes; however, the contribution of CD8(+) T cells against multicellular pathogen is still uncertain. The exogenous protein-pulsed dendritic cells (DCs) can easily activate CD4(+) T cells response, while CD8(+) T cells response was relatively difficult to be induced. In this study, we evaluated the immunogenicity of TSP2HD antigen (hydrophilic domain of the S. japonicum tetraspanin-2) and TAT (the protein transduction domain of HIV-1)-coupled TSP2HD protein. As TAT-fused protein could promote major histocompatibility complex class I-dependent antigen presentation in vitro, TAT-TSP2HD-pulsed DCs induced stronger proliferation of schistosome-specific CD8(+) T cells compared with DCs incubated with TSP2HD alone. Vaccination with TAT-TSP2HD-pulsed DCs in vivo could improve disease outcome in S. japonicum-infected mice and was slightly superior to vaccination with DCs treated with TSP2HD. In summary, these data showed that TAT fusion proteins could help activate CD8(+) cells and Th1 cells and provide part protection against schistosome.