Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen
Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen
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使用糖复合物抗原改变抗体对 HIV gp120 反应的特异性
DOI：
10.1021/acschembio.6b00224
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发表时间：
2016
影响因子：
4
通讯作者：
Ye Xin-Shan
中科院分区：
文献类型：
--
作者：
Liu Chang-Cheng;Zhai Canjia;Zheng Xiu-Jing;Ye Xin-Shan
HIV包膜蛋白上的一些保守聚糖是HIV广谱中和抗体（bnAb）的靶点。BnAb提供了HIV包膜蛋白上广泛中和表位的精确定义。这些表位对于疫苗设计是有希望的。许多与bnAb具有高亲和力的聚糖相关抗原已被测试为体内免疫原。然而，发现未诱导bnAb样抗体。用含有相同中和表位的不同免疫原接种可以增强集中于共享表位的抗体的亲和力成熟。这种联合免疫策略在基于肽表位的疫苗设计中显示了巨大的潜力。然而，迄今为止尚未对聚糖相关表位进行探索。在此，我们以2G12作为模型来验证聚糖相关表位的这种策略。将2G12的D1臂四甘露糖苷与牛血清白蛋白偶联，构建了高亲和力抗原。然后，将糖缀合物与重组gp120共免疫，预期其选择性地有益于诱导识别gp120上的2G12的中和表位的抗体。小鼠同时或交替接种两种抗原，以确定该策略的合适方案。血清学检测结果表明，与完整gp120结合的抗体滴度和亚型没有明显提高，与2G12表位竞争结合的抗体比例也没有明显提高。然而，共免疫的糖缀合物选择性地提高了识别gp120上D1臂四甘露糖苷相关结构的抗体的比例。这些结果为聚糖依赖性bnAb疫苗的设计提供了重要的经验。
Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogensin vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.