用合成糖肽模拟HIV广泛中和抗体表位。
Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
作者信息
Alam S Munir, Aussedat Baptiste, Vohra Yusuf, Meyerhoff R Ryan, Cale Evan M, Walkowicz William E, Radakovich Nathan A, Anasti Kara, Armand Lawrence, Parks Robert, Sutherland Laura, Scearce Richard, Joyce M Gordon, Pancera Marie, Druz Aliaksandr, Georgiev Ivelin S, Von Holle Tarra, Eaton Amanda, Fox Christopher, Reed Steven G, Louder Mark, Bailer Robert T, Morris Lynn, Abdool-Karim Salim S, Cohen Myron, Liao Hua-Xin, Montefiori David C, Park Peter K, Fernández-Tejada Alberto, Wiehe Kevin, Santra Sampa, Kepler Thomas B, Saunders Kevin O, Sodroski Joseph, Kwong Peter D, Mascola John R, Bonsignori Mattia, Moody M Anthony, Danishefsky Samuel, Haynes Barton F
机构信息
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
出版信息
Sci Transl Med. 2017 Mar 15;9(381). doi: 10.1126/scitranslmed.aai7521.
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man-V3). V3-glycan bnAbs bound to Man-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man-V3 induced V3-glycan-targeted antibodies. Thus, the Man-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
一种HIV-1疫苗的目标是通过诱导广泛中和抗体（bnAbs）来克服病毒变异性。bnAbs的一个关键靶点是包膜（Env）第三个可变环（V3）基部的聚糖-多肽。我们设计并合成了一种均一的最小免疫原，其具有反映天然Env V3-聚糖bnAb表位的高甘露糖聚糖（Man-V3）。V3-聚糖bnAbs以相似的亲和力与Man-V3糖肽和天然样gp140三聚体结合。荧光团标记的Man-V3糖肽与bnAb记忆B细胞结合，并能够用于从一名HIV-1感染个体中分离出一种V3-聚糖bnAb。在恒河猴中，用Man-V3免疫诱导了靶向V3-聚糖的抗体。因此，Man-V3糖肽紧密模拟HIV-1 V3-聚糖bnAb表位，可用于分离V3-聚糖bnAbs。
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