Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection

Abstract

Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins. Methods: In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from Schistosoma mansoni. This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner. Results: Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection. Conclusions: Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model.

Baseline Gut Microbiota Composition Is Associated With Schistosoma mansoni Infection Burden in Rodent Models

“…A total of 10 HMA and 10 WT (C57BL/6, bred at the WSI) mice were exposed to 80 S. mansoni cercariae ( Sm -exp), as described previously ( 22 ), and maintained for 50 days with access to food and water ad libitum . Additionally, 6 WT and HMA mice were kept uninfected and used as negative controls ( Sm -).…”

“…at days 28, 42, and 49 post-infection. At day 50 p.i., Sm -exp mice were euthanized, S. mansoni adult worms were recovered by portal perfusion, and livers removed for parasite egg counts ( 22 ). Briefly, liver sections from the right lobe were weighed and digested overnight in 3 ml of freshly prepared 4% KOH in 1x PBS, at 37°C under gentle agitation.…”

An invariantTrypanosoma vivaxvaccine antigen inducing protective immunity

“…Sera were transferred to streptavidin-coated ELISA plates on which the biotinylated target antigen was immobilised. To ensure that all anti-tag antibodies were adsorbed, binding of the lowest dilution of antisera was also tested against biotinylated rat Cd4d3+4-BLH protein similarly immobilised on the ELISA plate to confirm the absence of any anti-tag immunoreactivity 38 . Sera were incubated for one hour at room temperature followed by three washes with PBST before incubating with an anti-mouse IgG secondary antibody conjugated to alkaline phosphatase (Sigma) used as a 1:5000 dilution for one hour.…”

Daily rhythms in the transcriptomes of the human parasite Schistosoma mansoni

“…Thirty-six 6 weeks old female were percutaneously infected with 200 mixed-sex Schistosoma mansoni cercariae collected from 13 infected snails as described (Crosnier et al, 2019). In brief, under isoflurane anaesthesia, the mice were carefully transferred onto individual holders in a bespoke pre-warmed anaesthesia rig and their tails inserted into the test tubes containing with the cercariae.…”