Sugar epitopes as potential universal disease transmission blocking targets
Sugar epitopes as potential universal disease transmission blocking targets
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DOI：
10.1016/j.ibmb.2004.09.005
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发表时间：
2005-01-01
影响因子：
3.8
通讯作者：
Azad, AF
中科院分区：
文献类型：
--
作者：
Dinglasan, RR;Valenzuela, JG;Azad, AF
预防媒介传播疾病的一个有希望的方法是通过使用传播阻断疫苗（TBV）。然而，开发几种抗病原体TBV可能是不切实际的。在这项研究中，我们已经确定了一个保守的候选碳水化合物目标中肠的几个节肢动物载体。对新型GlycoChip（R）聚糖阵列的筛选发现，抗碳水化合物疟疾传播阻断单克隆抗体（MG 96）优先识别D-甘露糖（a）和11型乳糖胺二糖。采用α-甲基甘露糖苷作为抑制剂，通过竞争ELISA证实了对D-甘露糖的特异性。确定末端甘露糖残基的Con A不抑制MG 96与蚊子中肠裂解物的反应性，表明Con A对这种单糖具有差异识别。然而，杰克豆凝集素，Jacalin，其识别D-甘露糖（α），D-半乳糖（α/β）和T抗原，不仅显示出类似的带型识别MG 96的免疫印迹，但也显示出有效抑制MG 96。麦胚凝集素，它承认N-乙酰乳糖胺单位，只有部分抑制MG 96反应。这突出了两个聚糖部分对MG 96表位或糖表位的贡献。酶去糖基化结果表明，MG 96识别O-连接寡糖上的甘露糖α 1 -6取代。综上所述，数据表明MG 96识别节肢动物载体中肠上靠近Galbeta 1 - 4GlcNAc-α-O-R聚糖的Manalpha 1 -6组成的不连续糖表位。因此，这些糖表位可能代表广泛的媒介传播病原体的潜在传播阻断疫苗靶标。(C)2004爱思唯尔有限公司保留所有权利。
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.