Characterization of protective and non-protective surface membrane carbohydrate epitopes of Schistosoma mansoni

Abstract

We have produced a number of monoclonal antibodies, protective and non-protective, which recognize a complex of schistosomula antigens, including the 38 kDa antigen. Eight different protective and non-protective monoclonal antibodies, varying in isotypes, were used in the binding assays. Lectin inhibition studies suggested that the monoclonal antibodies probably recognized carbohydrate epitopes on the antigen(s). Immunoprecipitation studies showed that at least two of the monoclonal antibodies recognized different epitopes on the same molecule. Additionally, we tested for monoclonal antibody binding after the antigens were treated with; 1) proteases, 2) periodate, 3) various exo- and endoglycosidases, 4) mild acid hydrolysis. We also tested for binding of the antibodies to keyhole limpet hemocyanin (KLH). Using the 8 monoclonal antibodies as probes, we were able to define at least 4 different carbohydrate epitopes related to the protective monoclonal antibodies, and at least one epitope which is seen by the non-protective antibodies. The epitope seen by the non-protective antibodies was shown to be cross-reactive with epitopes on KLH. These results demonstrate the importance of epitope mapping studies for any defined vaccine.

Antibodies to Keyhole Limpet Hemocyanin Cross-React with an Epitope on the Polysaccharide Capsule of Cryptococcus neoformans and Other Carbohydrates: Implications for Vaccine Development

“…Recently, there have been reports cautioning against the use of KLH in the diagnosis of S. mansoni because Abs to KLH have been detected that are not specific to this parasite and crossreact with other worms, leading to false positives (60). In addition, KLH cross-reacts with nonprotective S. mansoni epitopes, and not the protective ones (10). Just as GXM contains protective and nonprotective epitopes, similar findings have been reported with other carbohydrate Ags (14,15).…”

A Schistosoma mansoni epitope recognized by a protective monoclonal antibody is identical to the stage-specific embryonic antigen 1.

“…As mentioned above, schistosome carbohydrate epitopes can induce both protective and blocking antibody responses. Blocking antibodies have been shown to inhibit in vivo (11) and in vitro (12) the action of protective antibodies, and they are believed to prevent the expression of immunity to reinfection particularly in young children (13 (4), others have demonstrated the ability of IgM antibodies against schistosomular surface antigens to confer significant levels of protection in vivo (9,(31)(32)(33). As no serious autoimmune complications have been seen with the administration of SSEA-1 antibodies (28), oligosaccharides containing the SSEA-1 trisaccharide could be tested as a potential basis for a defined vaccine that induces protective responses and does not elicit blocking antibodies.…”

“…We have generated (14) several monoclonal antibodies to the four major species of surface glycoproteins on S. mansoni cercaria and schistosomula, the invasive larval stages in the definitive vertebrate host; they recognize at least five distinct carbohydrate epitopes (9). Some of these antibodies confer protection against infection when passively administered to naive mice (6,9).…”

“…Some of these antibodies confer protection against infection when passively administered to naive mice (6,9). Because …”

The Immunologically Reactive O‐Linked Polysaccharide Chains Derived from Circulating Cathodic Antigen Isolated from the Human Blood Fluke Schistosoma Mansoni have Lewis x as Repeating Unit

“….) and ( -1 are for Fuc, Gal, and GlcNAc, respectively, to show magnetic dipole networks of (from top to bottom) Fuc CH,, GlcNAc NAc, Gal H-4, Gal H-I, GlcNAc H-1, Fuc H-5 and Fuc H-1.A letter-number combination near the cross-peaks refers to the proton(1)(2)(3)(4)(5)(6) of a monosaccharide residue (C, GlcNAc; F, Fuc; G, Gal), which has a NOE contact with the proton of the monosaccharide residue indicated at the corresponding diagonal peak. aFuc residue, namely Fuc H-1 at 6 5.118, H-5 at 6 4.805, and CH, at 6 1.145[56].…”