A MUCOSAL VACCINE WITH EPITOPES OF SCHISTOSOMA MANSONI
GLUTATHIONE S-TRANSFERASE GENETICALLY FUSED TO CHOLERA B SUBUNIT CONFERS
PROTECTION AGAINST INFECTION WITH SCHISTOSOMIASIS
Sun J-B1,
Lebens M1, Mielcarek M1, Li B-L1, Backstrom M1, Olsson I1, Capron A2,
Czerkinsky C3 and Holmgren J1
1 Department
of Medical Microbiology and Immunology, University of Goteborg, Guldhedsgatan 10A, SE-413 46 Goteborg, Sweden
2 Centre d'Immunologie et de Biologie Parasitaire,
INSERM U167, Institut Pasteur de Lille, France;
3 INSERM U
364, Nice, France
Objective: Schistosomiasis affects million children in developing countries and
its control by effective vaccination is a global health priority.
Methods: In this study intranasal administration of a peptide carrying tandemly
linked epitopes of Schistosoma mansoni 28kD glutathione-S-transferase (a.a.
24-43 and 191-212) genetically coupled to cholera toxin B subunit (CTB/GST)
was found to protect infected C57BL/6 mice with schistosomiasis.
Results: Treatment with CTB/GST significantly reduced both worm burden and
liver egg counts. These effects were associated with the induction of
Sm28GST-specific antibodies, predominantly IgG1 and IgG2a in serum. Local
IgE antibody responses were also found in the liver and lungs of the mice.
Moreover, marked suppression of granuloma formation in liver was observed
to associate with a reduction in systemic delayed type hypersensitivity
(DTH) and lymphocyte proliferative responses to egg antigens. Reduction in
hepatic production of IFN-gamma
and IL-4 were also observed.
Conclusions: These results point that therapeutic vaccine against schistosomiasis
based on peptides genetic-linked to mucosal binding molecule CTB can both
limit infection and independently suppress egg-induced pathology.