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

Academic Article

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.
  • Authors

  • Zhang, Weidong
  • Molehin, Adebayo J
  • Rojo, Juan
  • Sudduth, Justin
  • Ganapathy, Pramodh K
  • Kim, Eunjee
  • Siddiqui, Arif J
  • Freeborn, Jasmin
  • Sennoune, Souad R
  • May, Jordan
  • Lazarus, Samra
  • Nguyen, Catherine
  • Redman, Whitni K
  • Ahmad, Gul
  • Torben, Workineh
  • Karmakar, Souvik
  • Le, Loc
  • Kottapalli, Kameswara R
  • Kottapalli, Pratibha
  • Wolf, Roman F
  • Papin, James F
  • Carey, David
  • Gray, Sean A
  • Bergthold, Jenn D
  • Damian, Raymond T
  • Mayer, Bryan T
  • Marks, Florian
  • Reed, Steven G
  • Carter, Darrick
  • Siddiqui, Afzal A
  • Status

    Publication Date

  • August 2018
  • Keywords

  • Schistosoma mansoni
  • Sm-p80 vaccine
  • baboons
  • efficacy
  • schistosomiasis
  • systems biology
  • Digital Object Identifier (doi)

    Start Page

  • 38
  • End Page

  • 51
  • Volume

  • 1425
  • Issue

  • 1