C Crosnier4; M Roestenberg2; A Protasio4; C Brandt4; G Rinaldi4; C McCarthy4; J J Janse1; M C Langenberg1; S Clare4; C Hokke2; S Wilson3; M Berriman4; G J Wright4;
1 Leiden University Medical Center, Netherlands, Netherlands; 2 Leiden University Medical Centre, Netherlands; 3 University of Cambridge, UK; 4 Wellcome Sanger Institute, UK
DiscussionSchistosomiasis is a major global health problem caused by blood-dwelling parasitic worms. Infection of the human host starts with the penetration through the skin of free-swimming cercariae upon contact with contaminated water. The parasites first develop into schistosomula before maturing into adult worms that can survive for many years within their host’s bloodstream. Despite intensive efforts from the research community, only few vaccine candidates have progressed to clinical trials so far and treatment mostly relies on the mass administration of praziquantel in endemic areas. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and parasite burden, which, in regions of low transmission should be highly sensitive. With the aim to identifying new vaccine candidates and serological markers of infection, we have used proteomics and transcriptional data to compile a library of 115 S. mansoni cell surface and secreted proteins that we expressed recombinantly in mammalian cells. Overall, expression of 90% of the selected proteins could be detected by Western blot and the vast majority of them were shown to be immunoreactive and to contain heat-labile conformational epitopes when tested against pooled hyperimmune sera. Ninety-six of these proteins were used to immunise BALB/C mice in a systematic screen for the identification of new vaccine candidates. While most proteins triggered antibody titres with half-maximal reactivity > 1:10,000, none of them were associated with strong repeatable protection against reinfection. Using human and mouse sera from experimental infections, we were able to monitor the host humoral reactivity to 103 of these proteins and showed that members of the saposin-domain containing family were particularly antigenic, showing reactivity as early as five weeks post-infection. We envisage that this protein library will be useful to the wider scientific community to further understand Schistosoma biology.