Manipulation of the immune evasive properties of circulating cathodic antigen induces protective immunity against Schistosomiasis mansoni in C57BL/6 mice.

Schistosome circulating cathodic antigen (CCA) has been hypothesized to take part in immune evasion mechanisms that protect against host's immunity. To dissect its immunogenicity, lymphoproliferative responses of splenocytes were assessed in C57BL/6 mice immunized with recombinant plasmid constructs expressing full-length and truncated fragments of CCA cDNA, before and after challenge infection with S. mansoni cercariae. Prior to challenge, splenocytes of immunized mice showed low responses to phytohaemagglutinin (PHA) and high responses to native CCA, compared to controls. After challenge, PHA-responses increased on day 3 through day 7 and subsequently declined. On the other hand, CCA-induced responses increased on day 3 post-challenge then declined in mice immunized with CCA fragments lacking the N-terminus (-N CCA). Whereas, mice immunized with full-length or CCA fragment lacking the C-terminus (-C CCA) showed a delayed increase of CCA-induced responses that maximize on day 25. Interestingly, animals immunized with -N CCA showed a significant reduction in worm burden between 42-51%, while, mice immunized with full-length or -C CCA showed lower protection levels of about 15 and 37%, respectively. These findings suggest that CCA may contain immunosuppressive epitopes on the N-terminus. Abrogation of these epitopes could disrupt the immune evasion mechanism orchestrated by CCA, which could aid the development of an alternative vaccination approach.