The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-Å x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.

中文翻译：

---

一种天然产生的广泛而有效的 CD4 结合位点抗体，具有低体细胞突变

广泛中和抗体 (bNAb) 的诱导是针对 HIV-1 疫苗的潜在策略。然而，大多数 bNAb 表现出异常高的体细胞超突变等特征，包括插入和缺失，这使得它们的诱导具有挑战性。VRC01 类 bNAb 不仅表现出非凡的广度和效力，而且还跻身于最高体细胞突变的 bNAb 之列。在这里，我们描述了一种从病毒血症控制器 BG24 中分离出来的 VRC01 类抗体，该抗体的突变程度远低于同类抗体的大多数亲属，同时具有相当的广度和效力。BG24-BG505 Env 三聚体复合物的 3.8-Å x 射线晶体结构揭示了 vrc01 类 Abs 的 gp120 界面特征的保守接触，尽管缺乏常见的 CDR3 序列基序。