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

Accepted version
Peer-reviewed

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Type

Article

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Authors

Zhang, Weidong 
Molehin, Adebayo J 
Rojo, Juan U 
Sudduth, Justin 
Ganapathy, Pramodh K 

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.

Description

Keywords

Schistosoma mansoni, Sm-p80 vaccine, baboons, efficacy, schistosomiasis, systems biology, Animals, Female, Male, Antibodies, Protozoan, Double-Blind Method, Gene Expression Profiling, Papio, Parasite Egg Count, Protozoan Proteins, Protozoan Vaccines, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Schistosoma mansoni, Schistosomiasis, Transcription, Genetic

Journal Title

Ann N Y Acad Sci

Conference Name

Journal ISSN

0077-8923
1749-6632

Volume Title

1425

Publisher

Wiley