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

Academic Article

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.
  • Authors

  • Siddiqui, Arif J
  • Molehin, Adebayo J
  • Zhang, Weidong
  • Ganapathy, Pramodh K
  • Kim, Eunjee
  • Rojo, Juan
  • Redman, Whitni K
  • Sennoune, Souad R
  • Sudduth, Justin
  • Freeborn, Jasmin
  • Hunter, Derick
  • Kottapalli, Kameswara R
  • Kottapalli, Pratibha
  • Wettashinghe, Ruwanthi
  • van Dam, Govert J
  • Corstjens, Paul LAM
  • Papin, James F
  • Carey, David
  • Torben, Workineh
  • Ahmad, Gul
  • Siddiqui, Afzal A
  • Publication Date

  • June 11, 2018
  • Keywords

  • Schistosoma mansoni
  • Sm-p80 vaccine
  • differentially expressed genes (DEGs)
  • efficacy
  • praziquantel
  • schistosomiasis
  • systems biology
  • transcriptome
  • Digital Object Identifier (doi)

    Pubmed Id

  • 29888790
  • Start Page

  • 19
  • End Page

  • 37
  • Volume

  • 1425
  • Issue

  • 1