Use of an Sm-p80-based therapeutic vaccine to kill established adult schistosome parasites in chronically infected baboons

J Infect Dis. 2014 Jun 15;209(12):1929-40. doi: 10.1093/infdis/jiu031. Epub 2014 Jan 16.

Abstract

No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.

Keywords: Schistosoma mansoni; Schistosomiasis; Sm-p80; baboon; calpain; nonhuman primate; therapeutic vaccine.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Helminth / blood
  • Antibodies, Helminth / immunology
  • Antigens, Helminth / immunology*
  • B-Lymphocytes / immunology
  • Calpain / immunology*
  • Disease Models, Animal
  • Feces / parasitology
  • Female
  • Interferon-gamma / blood
  • Interleukin-17 / blood
  • Interleukin-4 / blood
  • Leukocytes, Mononuclear / immunology
  • Male
  • Papio / parasitology*
  • Parasite Egg Count
  • Schistosoma mansoni / drug effects
  • Schistosomiasis mansoni / drug therapy*
  • T-Lymphocytes / immunology
  • Vaccination
  • Vaccines / immunology*

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Interleukin-17
  • Vaccines
  • Interleukin-4
  • Interferon-gamma
  • Calpain