Intranasal administration of a Schistosoma mansoni glutathione S-transferase-cholera toxoid conjugate vaccine evokes antiparasitic and antipathological immunity in mice

Mucosal administration of Ags linked to cholera toxin B subunit (CTB) can i nduce both strong mucosal secretary IgA immune responses and peripheral T c ell hyporeactivity, In this study, intranasal (i.n.) administration of CTB- conjugated Schistosoma mansoni 28-kDa GST (CTB-Sm28GST) was found to protec t 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 co njugate as compared with mice infected only, or with mice treated with a co ntrol (CTB-OVA) conjugate, However, a more striking and consistent effect w as that granuloma formations in liver and lungs of mice treated with CTB-Sm 28GST were markedly suppressed, Such treatment was associated with reduced systemic delayed-type hypersensitivity and lymphocyte proliferative respons es to Sm28GST, Production of IFN-gamma, IL-3, and IL-5 by liver cells was a lso markedly reduced after i.n. treatment of CTB-Sm28GST, whereas IL-4 prod uction was not impaired. Intranasal treatment of infected mice with CTB-Sm2 8GST increased IgG1-, IgG2a-, IgA-, and IgE-Ab-forming cell responses in li ver in comparison with treatment with CTB-OVA, or free Sm28GST. Most import antly, mucosal treatment with CTB-Sm28GST significantly reduced animal mort ality when administered to chronically infected mice. Our results suggest t hat it may be possible to design a therapeutic vaccine against schistosomia sis that both limits infection and suppresses parasite-induced pathology.