期刊
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 35, 期 1, 页码 1-10出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ibmb.2004.09.005
关键词
carbohydrate; transmission blocking vaccine; mosquito; midget; vector-borne disease
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000932, Z01AI000932] Funding Source: NIH RePORTER
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(R) glycan array found that the anti-carbohydrate malaria transmission blocking monoclonal antibody (MG96) preferentially recognized D-mannose (a) and the type 11 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. (C) 2004 Elsevier Ltd. All rights reserved.
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