Human schistosomiasis caused by parasitic flatworms of the genus Schistosoma remains an important public health problem in spite of concerted efforts at control. An effective vaccine would be a useful addition to control strategies that currently rely on chemotherapy, but such a product is not imminent. In this review, likely causes for the lack of progress are first considered. These include the strategies used by worms to evade the immune response, concepts that have misdirected the field, an emphasis on internal antigens, and the use of the laboratory mouse for vaccine testing. On a positive note, recent investigations on self-cure by the rhesus macaque offer the most promising context for vaccine development. The identification of proteins at the parasite–host interface, especially those of the esophageal glands involved in blood processing, has provided an entirely new category of vaccine candidates that merit evaluation.

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