Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design.
Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design.
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DOI：
10.1016/j.immuni.2015.10.014
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发表时间：
2015-11-17
期刊：
影响因子：
32.4
通讯作者：
Burton DR
中科院分区：
文献类型：
--
作者：
Andrabi R;Voss JE;Liang CH;Briney B;McCoy LE;Wu CY;Wong CH;Poignard P;Burton DR
针对HIV包膜(Env)三聚体V2尖端的广谱中和抗体(BNAbs)从个体HIV感染者中分离出来，能有效中和不同的HIV毒株，但设计免疫原以诱导bNAbs的策略尚未确定。在这里，我们比较了V2顶端bNAbs的四个原型(PG9，CH01，PGT145和CAP256，VRC26.09)，结果表明它们都识别V2碱性残基的核心表位和糖链-N160。两个原型bNAb来自VH胚系，它们99%相同，并使用共同的胚系D基因编码的YYD基序与V2表位相互作用。我们从三个原型bNAbs中鉴定了被IGL中和的病毒，来自其中一个分离物的可溶性Env被证明形成了一个有序的Env三聚体，它模仿病毒粒子表面的三聚体，并可以启动V2-顶端的bNab反应。这些研究说明了一种从bNAb小组过渡到候选疫苗的战略。
Broadly neutralizing antibodies (bnAbs) directed to the V2 apex of the HIV envelope (Env) trimer isolated from individual HIV-infected donors potently neutralize diverse HIV strains, but strategies for designing immunogens to elicit bnAbs have not been identified. Here, we compared four prototypes (PG9, CH01, PGT145 and CAP256.VRC26.09) of V2 apex bnAbs and showed that all recognized a core epitope of basic V2 residues and the glycan-N160. Two prototype bnAbs were derived from VH-germlines that were 99% identical and used a common germline D-gene encoded YYD-motif to interact with the V2-epitope. We identified viruses that were neutralized by iGL from three prototype bnAbs and soluble Env derived from one of the isolates was shown to form a well-ordered Env trimer that mimics that on the surface of virions and could serve to initiate a V2-apex bnAb response. These studies illustrate a strategy to transition from panels of bnAbs to vaccine candidates.