Sm‐p80‐based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re‐encounter

Abstract

Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection.

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

“…14,15 To develop a viable schistosomiasis vaccine, the efficacy of an Sm-p80-based vaccine was systematically evaluated in baboons (Papio anubis), natural hosts of schistosomiasis and the most relevant nonhuman primate model of human clinical man-ifestations of both acute and chronic disease. [16][17][18] Sm-p80 is the heavy chain of the S. mansoni calcium activated neutral protease (calpain), and is the only classical calpain among the nonhuman calpains. 19,20 Sm-p80 meets the requirements for a suitable schistosome vaccine candidate because it is present in the surface membranes and epithelial syncytium of the worm, 21,22 it is one of the immunodominant membrane antigens, 22 and it displays no immunological cross-reactivity with human or other vertebrate calpains.…”

Schistosomiasis vaccine development: update on human clinical trials

“…The authors also reported a significant reduction in hatching rates of eggs excreted in feces [48]. In another recent study designed to mimic field scenario of schistosomiasis vaccine deployment, it was shown that Sm-p80-based vaccination following PZQ treatment of chronically-infected baboons caused a significant reduction in tissue egg retention and hatching rates when subsequently challenged with S. mansoni cercariae [49]. Notably, infected human populations tested to date have not been shown to express Sm-p80-specific IgE antibodies [50,51] thereby lessening the potential risk of severe allergic reaction.…”

Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

“…Immunization of an individual is likely to be achieved with multiple vaccine doses spread across a number of weeks [14], dependent on vaccine characteristics and logistical factors. Given this uncertainty, we made the simplifying assumption that immunization occurs instantaneously at a specified time point.…”

“…In keeping with recent trials of Sm-p80 vaccines in baboons, we made three key assumptions about the vaccine [14]. We assumed the vaccine does not have a therapeutic effect on already established schistosomes, i.e.…”