TheSchistoVac is a FP7-HEALTH-2009 Collaborative project funded by the European Commission, running from Feb 2010 - 31 July 2014, coordinated by Leiden University Medical Center.

Summary of the project and its main achievements

Schistosomiasis is an exceptionally chronic infection caused by the trematode worms of Schistosoma mansoni, S. haematobium and S. japonicum. More than 200 million people in many of the most resource‐deprived regions of the developing world are chronically infected with blood‐dwelling schistosome worms. Infection with these worms can cause chronic debilitating morbidity and result in a massive economic and social burden that is often underestimated, and treatment does not prevent reinfection, indicating a real need for a vaccine. The objectives of TheSchistoVac, carried out by a unique consortium of European and African participants, are to identify molecules on the skin stage schistosomula that can induce protective immune responses. Candidates selected from post-genomic analysis which are recognized by antibodies in human sera collected in endemic African areas were produced as recombinant proteins. These candidates were tested in in vitro parasite opsonisation assays and an in vivo models of vaccination in rats. Uniquely, the reactivity of candidate antigens at the cellular level with human T and B cells was as assessed using samples from newly collected endemic cohorts to discover protective cellular responses. The combined data point out a number of novel vaccine candidates that may be developed into an effective prophylactic vaccine against schistosome infections. By intense training and exchange programs between the participants of the project TheSchistoVac supported the formation of a nucleus of African scientists in helminth vaccine development.

The main findings, achievements and impact of TheSchistoVac are:

• Selection of promising candidates by antibody screening of defined resistant and susceptible populations. Both protein and glycan targets giving robust IgG responses have been identified by HT antibody screening. All are of potential interest for further vaccine development research.
• Definition of responses to candidate antigens by T cells of endemic population classified as resistant and susceptible. Our data suggests that a higher ratio of Th1/Th2 or pro/anti-inflammatory cytokines in response to specific candidate antigens correlates with resistant phenotype. The most promising candidates on basis to the cellular work are SmSP7 and SmLy6b/CD59b.
• Pre‐clinical in vivo testing in the rat vaccination model indicates that SmKK7 and a specific glycan type are the most promising candidates. These and the candidates indicated by cellular work will be useful starting points for further pre-clinical and ultimately clinical vaccine development.
• Clearly, different candidates for a vaccine against Schistosoma mansoni infection were selected on the basis of different in vitro and in vivo tests designed to correlate different aspects of the immune response with protective potential. These candidates should be further developed pre-clinically, ideally by comparison with benchmark candidates such as SmTSP-2 in the same tests.
• Regulatory T-cell numbers in infected subjects decrease upon chemotherapy, indicating that current infections prevent efficient T-cell response to vaccination.
• Schistosome infection is associated with regulatory B cells and with memory B cells that both can contribute prolonging parasite survival.
• A template for development of vaccines against S. haematobium and S. japonicum. The established pipeline for S. mansoni, and the identification of homologous proteins in other schistosome species has provided a development platform.
• TheSchistoVac results led to the advancement of immunological understanding of schistosomiasis (innate and adaptive immunity).
• TheSchistoVac led to improvements in rational vaccine design in schistosomiasis and other helminth infections.
• TheSchistoVac has significantly contributed to sustained and integrated helminth research in Sub‐Saharan Africa.