title: Sugar epitopes as potential universal disease transmission blocking targets.
abstract: One promising method to prevent vector-borne diseases is through the use of transmission blocking vaccines (TBVs). However, developing several anti-pathogen TBVs may be impractical. In this study, we have identified a conserved candidate carbohydrate target in the midguts of several Arthropod vectors. A screen of the novel GlycoChip glycan array found that the anti-carbohydrate malaria transmission blocking monoclonal antibody (MG96) preferentially recognized D-mannose (alpha) and the type II lactosamine disaccharide. The specificity for D-mannose was confirmed by competition ELISA using alpha-methyl mannoside as inhibitor. Con A, which identifies terminal mannose residues, did not inhibit MG96 reactivity with mosquito midgut lysates, suggesting that Con A has differential recognition of this monosaccharide. However, the jack bean lectin, Jacalin, which recognizes D-mannose (alpha), d-galactose (alpha/beta) and the T antigen, not only displays a similar banding profile to that recognized by MG96 on immunoblot but was also shown to effectively inhibit MG96. Wheat-germ agglutinin, which recognizes N-acetyllactosamine units, only partially inhibited MG96 reactivity. This highlights the contribution of both glycan moieties to the MG96 epitope or glycotope. Enzyme deglycosylation results suggest that MG96 recognizes a mannose alpha1-6 substitution on an O-linked oligosaccharide. Taken together, the data suggest that MG96 recognizes a discontinuous glycotope composed of Manalpha1-6 proximal to Galbeta1-4GlcNAc-alpha-O-R glycans on arthropod vector midguts. As such, these glycotopes may represent potential transmission blocking vaccine targets for a wide range of vector-borne pathogens.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Rhoel R
authors.initials: RR
authors.lastname: Dinglasan
authors.forename: Jesús G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Abdu F
authors.initials: AF
authors.lastname: Azad
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000276:immunology*; D001096:Arachnid Vectors / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D003870:Dermacentor / Q000276:immunology; D004064:Digestive System / Q000276:immunology; D000939:Epitopes; D005260:Female; D008288:Malaria; D008297:Male; D008358:Mannose / Q000276:immunology; D005423:Siphonaptera / Q000276:immunology; D014224:Triatoma / Q000276:immunology; D014370:Tsetse Flies / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D002241:Carbohydrates; D000939:Epitopes; D014612:Vaccines; D008358:Mannose