Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.

Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
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DOI:
10.1126/scitranslmed.aai7521
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发表时间:
2017-03-15
影响因子:
17.1
通讯作者:
Haynes BF
Haynes BF
中科院分区:
医学1区
文献类型:
--
作者:
Alam SM;Aussedat B;Vohra Y;Meyerhoff RR;Cale EM;Walkowicz WE;Radakovich NA;Anasti K;Armand L;Parks R;Sutherland L;Scearce R;Joyce MG;Pancera M;Druz A;Georgiev IS;Von Holle T;Eaton A;Fox C;Reed SG;Louder M;Bailer RT;Morris L;Abdool-Karim SS;Cohen M;Liao HX;Montefiori DC;Park PK;Fernández-Tejada A;Wiehe K;Santra S;Kepler TB;Saunders KO;Sodroski J;Kwong PD;Mascola JR;Bonsignori M;Moody MA;Danishefsky S;Haynes BF

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HIV-1疫苗的目标是通过诱导广泛中和抗体(bnAb)来克服病毒变异性。bnAb的一个关键靶标是包膜(Env)第三可变环(V3)底部的聚糖多肽。我们设计并合成了具有反映天然Env V3-聚糖bnAb表位(Man 9-V3)的高甘露糖聚糖的同质最小免疫原。V3-聚糖bnAb以相似的亲和力结合Man 9-V3糖肽和天然样gp 140三聚体。荧光团标记的Man 9-V3糖肽结合bnAb记忆B细胞,并能够用于从HIV-1感染个体中分离V3-聚糖bnAb。在恒河猴中,用Man 9-V3免疫诱导V3聚糖靶向抗体。因此,Man 9-V3糖肽紧密模拟HIV-I V3-聚糖bnAb表位,并且可用于分离V3-聚糖bnAb。
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 (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-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 Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
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