Table 1. Road blocks to schistosome vaccine development and how controlled human infection models for schistosomiasis can help.

(CHI-S) - Controlled human infection model for Schistosoma mansoni.

Road blocks		How CHI-S can help
Vaccine candidates: Several vaccine candidates are available; but • there are limited resources to take candidates forward • the focal and dynamic epidemiology of schistosomiasis may make efficacy studies difficult • the requirement for pretreatment of subjects before vaccine testing can influence epidemiology and complicate the efficacy evaluation		✓   CHI-S quickly identifies candidates most likely to induce protection  ✓   CHI-S can be performed in populations with defined pre-exposure
Animal models: Suitability of various animals for predicting responses to, and efficacy of, vaccine candidates in humans not known		✓   CHI-S provides direct evidence of responses in humans
Immunological road-blocks: •   Schistosomes induce regulatory responses which could impair vaccine immunogenicity •   Schistosomes induce Th2 responses and IgE with accompanying risk of allergic phenomena •   Th1 responses involved in protection not known in humans •   Correlates of protection not known		✓   CHI-S describes evolution of immune responses following infection  ✓   Combined with a model “vaccine” (such as irradiated cercariae, predicted to be effective) CHI-S identifies protective Th1 responses and correlates of protection