来自美国斯克里普斯研究所的科学家描述了抗体识别和中和HIV细节，揭示了HIV病毒的一个重大弱点，为HIV疫苗研发提供了一个新靶点。相关研究近日发表在《科学》网络版上。
在这项研究中，一种名为PGT 128的抗体能够非常有效地中和HIV。通过X射线晶体学方法，研究者确定了PGT 128的结构。有了这些结构数据，通过改变HIV目标位点，可以观察到PGT 128通过部分与HIV表面多聚糖结合来发挥作用。多聚糖通常覆盖HIV表面，保护HIV，抵御免疫系统攻击。但是，PGT 128能够结合两个相近的多聚糖，并同时接触到其余多聚糖。这说明PGT 128抗原表位很容易进入HIV。
该论文通讯作者Dennis Burton表示，PGT 128为我们研发HIV疫苗展示了一个很好的靶点。（生物谷 Bioon.com）
doi:10.1126/science.1213256
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A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield
Pejchal, Robert; Doores, Katie J.; Walker, Laura M.; Khayat, Reza; Huang, Po-Ssu; Wang, Sheng-Kai; Stanfield, Robyn L.; Julien, Jean-Philippe; Ramos, Alejandra; Crispin, Max; Depetris, Rafael; Katpally, Umesh; Marozsan, Andre; Cupo, Albert; Maloveste, Sebastien; Liu, Yan; McBride, Ryan; Ito, Yukishige; Sanders, Rogier W.; Ogohara, Cassandra; Paulson, James C.; Feizi, Ten; Scanlan, Christopher N.; Wong, Chi-Huey; Moore, John P.; Olson, William C.; Ward, Andrew B.; Poignard, Pascal; Schief, Willia
The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of Fabs PGT 127 and 128 with Man9 at 1.65 and 1.29 Å resolution, respectively, and glycan binding data delineate a specific high mannose binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 Å reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 IgGs may be mediated by cross-linking Env trimers on the viral surface.
