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*
Department of Medical Microbiology and Immunology, University of Göteborg, Göteborg, Sweden;
Centre d’Immunologie et de Biologie Parasitaire, Institut National de la Santé et de la Recherche Médicale U167, Institut Pasteur de Lille, Lille, France;
Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia; and
§
Institut National de la Santé et de la Recherche Médicale U364, Nice, France
Mucosal administration of Ags linked to cholera toxin B subunit
(CTB) can induce both strong mucosal secretory IgA immune responses and
peripheral T cell hyporeactivity. In this study, intranasal (i.n.)
administration of CTB-conjugated Schistosoma mansoni
28-kDa GST (CTB-Sm28GST) was found to protect infected animals from
schistosomiasis, especially from immunopathological complications
associated with chronic inflammation. Worm burden and liver egg counts
were reduced in infected animals treated with the CTB-Sm28GST conjugate
as compared with mice infected only, or with mice treated with a
control (CTB-OVA) conjugate. However, a more striking and consistent
effect was that granuloma formations in liver and lungs of mice treated
with CTB-Sm28GST were markedly suppressed. Such treatment was
associated with reduced systemic delayed-type hypersensitivity and
lymphocyte proliferative responses to Sm28GST. Production of IFN-
,
IL-3, and IL-5 by liver cells was also markedly reduced after i.n.
treatment of CTB-Sm28GST, whereas IL-4 production was not impaired.
Intranasal treatment of infected mice with CTB-Sm28GST increased IgG1-,
IgG2a-, IgA-, and IgE-Ab-forming cell responses in liver in comparison
with treatment with CTB-OVA, or free Sm28GST. Most importantly, mucosal
treatment with CTB-Sm28GST significantly reduced animal mortality when
administered to chronically infected mice. Our results suggest that it
may be possible to design a therapeutic vaccine against schistosomiasis
that both limits infection and suppresses parasite-induced
pathology.
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