Lacto-N-fucopentaose III Found on Schitosoma mansoni Egg Antigens Functions as Adjuvant for Proteins by Inducing Th2-Type Response

摘要

We have recently demonstrated that induction of Th2 responses by Schistosoma mansoni egg Ag is largely due to carbohydrates on the Ag functioning as adjuvants. Lacto-N-fucopentaose III (LNFP111), a polylactosamine sugar, is the predominant carbohy. drate found in So mansoni egg Ag. Therefore, using neoglycoprotein, we investigated whether LNFP111 induces in vivo Th2 response and functions as an adjuvant. Following intranasal immunization with LNFP111linked to human serum albumin (HSA) (HSA-LNFP111), 8AL8/c mice mounted a strong Th2 response and produced significantly higher levels of total IgE as well as HSA-specific IgG, IgG1, and IgE. HSA-LNFP111 was over 1000-fold more potent in inducing Ab production as compared with HSA alone. Although LNFP111 itself did not function as an epitope for either IgG or IgE, its conjugation with protein was essential for the adjuvant activity. Moreover, fucose residue on LNFP111 was crucial for induction of Ab production. Nasal lymphocytes from mice immunized with HSA-LNFP111 produced IL-4, IL-5, and IL-10, but not IFN-y following in vitro stimulation with HSA or HSA-LNFP111. In addition, these activated nasal lymphocytes also showed a significant increase of 87-2 expression on 8220. positive cells. Furthermore, not only intranasal but also both i.p. and s.c. immunization with HSA-LNFPIII induced significant production of HSA-specific Abs compared with the immunization with HSA alone, suggesting that the activity of LNFPIII was not restricted on particular route of immunization. These results demonstrate that Lewis type carbohydrate LNFP111 can function as an adjuvant by their ability to induce a Th2 response.