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

Abstract

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 (LNFPIII), a polylactosamine sugar, is the predominant carbohydrate found in S. mansoni egg Ag. Therefore, using neoglycoprotein, we investigated whether LNFPIII induces in vivo Th2 response and functions as an adjuvant. Following intranasal immunization with LNFPIII linked to human serum albumin (HSA) (HSA-LNFPIII), BALB/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-LNFPIII was over 1000-fold more potent in inducing Ab production as compared with HSA alone. Although LNFPIII 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 LNFPIII was crucial for induction of Ab production. Nasal lymphocytes from mice immunized with HSA-LNFPIII produced IL-4, IL-5, and IL-10, but not IFN-γ following in vitro stimulation with HSA or HSA-LNFPIII. In addition, these activated nasal lymphocytes also showed a significant increase of B7-2 expression on B220-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 LNFPIII can function as an adjuvant by their ability to induce a Th2 response.

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

“…Binding of SEA to DC-SIGN is dependent on the sugar motifs Le x and LDN-F [17], while chemical modification of the glycans present in SEA abolishes the Th2-driving capacity of SEA [19]. This, together with the observation that Le x -containing LNFPIII favors Th2-biased responses [20], suggests that CLR play an important role in conditioning DC for induction of Th2 responses by schistosomal antigens. Moreover, antigens from Toxocara canis were found to be recognized by DC-SIGN expressed on DC [21], and the induction of a Th2 response in vivo by antigens of the parasitic nematode Brugia malayi, as well as the free-living nematode Caenorhabditis elegans, was found to be dependent on intact glycans [22].…”

“…For instance, SEA, which contains glycoproteins, is recognized and internalized by human DC in a DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN)-, mannose receptor-and macrophage galactose-type lectin-dependent manner [16,17] [20], suggests that CLR play an important role in conditioning DC for induction of Th2 responses by schistosomal antigens. Moreover, antigens from Toxocara canis were found to be recognized by DC-SIGN expressed on DC [21], and the induction of a Th2 response in vivo by antigens of the parasitic nematode Brugia malayi, as well as the free-living nematode Caenorhabditis elegans, was found to be dependent on intact glycans [22].…”

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

“…There are some S. mansoni antigens described in the literature, such as LNFPIII (Okano et al 2001, Thomas et al 2003 and fosfatidilserine (PS) (van der Kleij et al 2004) that also induce IL-10 production by the cells from the innate im- Fig. 2: production of IL-10 by PBMCs of individuals chronically infected with Schistosoma mansoni stimulated in vitro with S. mansoni antigens (10 µg/ml).…”

Recombinant Ov-ASP-1, a Th1-Biased Protein Adjuvant Derived from the Helminth Onchocerca volvulus, Can Directly Bind and Activate Antigen-Presenting Cells

“…Some of these molecules were shown to contain pathogen associated molecular patterns (PAMP) 4 that bind to endocytic-pattern recognition receptors on APCs. Several helminth products were also reported to act as adjuvants in experimental vaccine models, but they preferentially induced Th2-type immune responses (5)(6)(7)(8).…”

“…Similarly, lacto-N-fucopentaose III, a carbohydrate found on the surface of the eggs of a human parasite, Schistosoma mansoni, acted as a Th2 adjuvant for human serum albumin when injected intranasally, s.c., or i.p. into mice (6,7). In a recent report, a 19 aa synthetic peptide (GK-1) from Taenia crassiceps cysticerci was shown to also have a capacity of an adjuvant (8).…”