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. [ABSTRACT FROM AUTHOR]