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

Ann N Y Acad Sci. 2018 Aug;1425(1):38-51. doi: 10.1111/nyas.13942.

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.

Keywords: Schistosoma mansoni; Sm-p80 vaccine; baboons; efficacy; schistosomiasis; systems biology.

Publication types

  • Clinical Trial, Veterinary
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antibodies, Protozoan / immunology
  • Double-Blind Method
  • Female
  • Gene Expression Profiling
  • Male
  • Papio
  • Parasite Egg Count
  • Protozoan Proteins / immunology
  • Protozoan Vaccines / administration & dosage*
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Schistosoma mansoni / immunology
  • Schistosomiasis / prevention & control*
  • Schistosomiasis / transmission
  • Schistosomiasis / veterinary*
  • Transcription, Genetic

Substances

  • Antibodies, Protozoan
  • Protozoan Proteins
  • Protozoan Vaccines