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

Ann N Y Acad Sci. 2018 Aug;1425(1):19-37. doi: 10.1111/nyas.13866. Epub 2018 Jun 11.

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.

Keywords: Schistosoma mansoni; Sm-p80 vaccine; differentially expressed genes (DEGs); efficacy; praziquantel; schistosomiasis; systems biology; transcriptome.

Publication types

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

MeSH terms

  • Animals
  • Anthelmintics / therapeutic use
  • Antibodies, Helminth / immunology
  • Antigens, Helminth / immunology
  • Chronic Disease
  • Female
  • Humans
  • Male
  • Parasite Egg Count
  • Praziquantel / therapeutic use*
  • Schistosoma mansoni / drug effects
  • Schistosoma mansoni / immunology*
  • Schistosoma mansoni / physiology
  • Schistosomiasis mansoni / immunology*
  • Schistosomiasis mansoni / parasitology
  • Schistosomiasis mansoni / therapy
  • Treatment Outcome
  • Vaccination / methods*
  • Vaccines / administration & dosage
  • Vaccines / immunology*

Substances

  • Anthelmintics
  • Antibodies, Helminth
  • Antigens, Helminth
  • Vaccines
  • Praziquantel