Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response

Vaccine. 2012 Jan 20;30(5):862-71. doi: 10.1016/j.vaccine.2011.11.110. Epub 2011 Dec 13.

Abstract

The control of strongyloidiasis affecting approximately 100 million people - caused by the gastrointestinal nematode Strongyloides stercoralis - is still based on anti-helminthic treatment. In the current study we analysed the immune response to Strongyloides ratti heat shock protein 60 (srHSP60) as a possible vaccine candidate in the murine system. We show that srHSP60 is a target of both, humoral and cellular response in S. ratti-infected mice. Strikingly, vaccination with srHSP60 without adjuvant or with CFA induced a S. ratti-specific Th1 response in vivo that did not confer protection but slightly increased larval output during challenge infection. Using in vitro T cell stimulation assays we provide further evidence that srHSP60 skewed activated T cells towards a Th1 response that interfered with efficient clearance of S. ratti infection. Vaccination with alum-precipitated srHSP60, in contrast, overruled the Th1-inducing activity intrinsic to srHSP60, induced a Th2 response, and conferred partial protection against a challenge infection. As srHSP60 is actively secreted by S. ratti during all life stages, our findings strongly suggest that srHSP60 induced polarization towards a Th1 response reflects a mechanism of immune evasion by this pathogenic nematode.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Alum Compounds / administration & dosage
  • Animals
  • Antigens, Helminth / administration & dosage
  • Antigens, Helminth / immunology*
  • Antigens, Helminth / isolation & purification
  • Chaperonin 60 / administration & dosage
  • Chaperonin 60 / immunology*
  • Chaperonin 60 / isolation & purification
  • Disease Models, Animal
  • Disease Susceptibility*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Strongyloides ratti / immunology*
  • Strongyloidiasis / immunology
  • Strongyloidiasis / parasitology
  • Strongyloidiasis / prevention & control*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology
  • Vaccination / methods*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antigens, Helminth
  • Chaperonin 60
  • aluminum sulfate