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

Abstract

Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

Schistosomiasis vaccine development: update on human clinical trials

“…Data from several murine and nonhuman primate studies showed prophylactic, therapeutic, anti-pathology and transmission-blocking efficacies as demonstrated by significant reduction in adult worms, killing of established worms [47], reduction in tissue egg load and fecal egg excretion [14]. Recently, in a double-blind preclinical trial, baboons immunized with Sm-p80/GLA-SE had a 93.45% reduction in adult female worms with a consequent 89.95% reduction in tissue egg load [48]. The authors also reported a significant reduction in hatching rates of eggs excreted in feces [48].…”

“…Recently, in a double-blind preclinical trial, baboons immunized with Sm-p80/GLA-SE had a 93.45% reduction in adult female worms with a consequent 89.95% reduction in tissue egg load [48]. 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].…”

Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates

“…In this study, baboons selected for the co-infection group did not undergo deworming and specific-pathogen-free baboons were utilized for the single infection group. We subsequently exposed all baboons to 1000 S. mansoni cercariae percutaneously as previously described [7]. Eight weeks after infection with S. mansoni, necropsies were performed.…”

“…For determination of schistosome egg burden in tissue, liver samples were digested overnight in 4% potassium hydroxide at 37 °C without CO 2 . This suspension was then washed and resuspended with a solution of 1.2% (w/v) NaCl and eggs were enumerated under light microscopy to determine the number of eggs per gram of tissue [7]. Excised spleen samples and mesenteric lymph nodes were mashed through nylon cell strainers and stored in freezing media until RNA purification for RNA-sequencing.…”

T cell mediated immunity to Schistosoma japonicum infection and vaccination

“…Furthermore, it has also been shown that Sm-p80 has a therapeutic effect in vaccinated baboons through decreasing the numbers of established worms, reducing the retention of eggs in tissues and decreasing the number of eggs excreted in faeces [112]. More recent data on recombinant Sm-p80 showed a worm reduction of 33.33% -53.13% and 38% in mice and baboon respectively [113,114] and also in baboon significant reduction in hepatic egg (67.7%) [115] and 93.45% reduction on pathology producing female worms was reported [116]. Moreover, vaccine immunogenicity of Sm-p80 was assessed using RNA sequencing and it is revealed that the vaccine candidate induced both cellular and humoral immune response and a predominant Th1,Th2 and Th17 gene signature was obtained [117].…”