來自美國(guó)斯克里普斯研究所的科學(xué)家描述了抗體識(shí)別和中和HIV細(xì)節(jié)，揭示了HIV病毒的一個(gè)重大弱點(diǎn)，為HIV疫苗研發(fā)提供了一個(gè)新靶點(diǎn),。相關(guān)研究近日發(fā)表在《科學(xué)》網(wǎng)絡(luò)版上,。
在這項(xiàng)研究中，一種名為PGT 128的抗體能夠非常有效地中和HIV,。通過X射線晶體學(xué)方法,，研究者確定了PGT 128的結(jié)構(gòu)。有了這些結(jié)構(gòu)數(shù)據(jù),，通過改變HIV目標(biāo)位點(diǎn),，可以觀察到PGT 128通過部分與HIV表面多聚糖結(jié)合來發(fā)揮作用。多聚糖通常覆蓋HIV表面,，保護(hù)HIV,，抵御免疫系統(tǒng)攻擊。但是,，PGT 128能夠結(jié)合兩個(gè)相近的多聚糖,，并同時(shí)接觸到其余多聚糖。這說明PGT 128抗原表位很容易進(jìn)入HIV,。
該論文通訊作者Dennis Burton表示，PGT 128為我們研發(fā)HIV疫苗展示了一個(gè)很好的靶點(diǎn),。（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.
