Toward a carbohydrate-based HIV-1 vaccine: Synthesis and immunological studies of oligomannose-containing glycoconjugates
Toward a carbohydrate-based HIV-1 vaccine: Synthesis and immunological studies of oligomannose-containing glycoconjugates
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DOI：
10.1021/bc0502816
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Wang, LX
中科院分区：
文献类型：
--
作者：
Ni, JH;Song, HJ;Wang, LX
人抗体 2G12 是一种广泛中和抗体，通过靶向 HIV-1 gp120 上的新型寡甘露糖簇来发挥其抗 HIV 活性。先前已证明合成的寡甘露糖簇可以模拟2G12的碳水化合物表位并表现出增强的抗原性(Wang L.X.等人(2004)Chem.Biol.11, 127)。本文描述了含有低聚甘露糖的糖复合物的合成，其中包括载体蛋白或通用 T 辅助表位肽，以提供有效的免疫原。结果表明，含有低聚甘露糖簇的合成新糖缀合物可以被人抗体2G12识别。兔免疫研究表明，只有一小部分由糖缀合物产生的抗体针对碳水化合物抗原，而大多数 IgG 型抗体针对缀合物中的接头。抗血清与 HIV-1 gp120 表现出弱交叉反应性。
Human antibody 2G12 is a broadly neutralizing antibody that exerts its anti-HIV activity by targeting a novel oligomannose cluster on HIV-1 gp120. It was previously demonstrated that synthetic oligomannose clusters could mimic the carbohydrate epitope of 2G12 and showed enhanced antigenicity (Wang L. X. et al. (2004) Chem. Biol. 11, 127). This paper describes the synthesis of oligomannose-containing glycoconjugates that include either a carrier protein or a universal T-helper epitope peptide to provide an effective immunogen. It was shown that the synthetic neoglycoconjugates containing oligomannose clusters could be recognized by the human antibody 2G12. Rabbit immunization studies revealed that only a small fraction of antibodies raised by the glycoconjugates was directed to the carbohydrate antigens, with the majority of the IgG type antibodies being directed to the linkers in the conjugates. The anti-sera showed weak cross-reactivity to HIV-1 gp120.