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

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.

• Authors: Nadia Ben Nouir, Marie-Luise Eschbach, Melanie Piédavent, Anke Osterloh, Manchang Tanyi Kingsley, Klaus Erttmann, Norbert Brattig, Eva Liebau, Bernhard Fleischer, Minka Breloer
• Journal: Vaccine (Vaccine) Vol. 30 Issue 5 Pg. 862-71 (Jan 20 2012) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 22172506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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