Data set for "Precise targeting of HIV broadly neutralizing antibody precursors in humans"

Data set: A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01B, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.

数据集：一款预防性人类免疫缺陷病毒（HIV）疫苗需在人体内诱导广谱中和抗体（broadly neutralizing antibodies, bnAbs），但激活稀有bnAb前体B细胞始终是极具挑战性的难题。在一项双盲、安慰剂对照的I期人体临床试验中，采用AS01B佐剂的重组靶向生殖系包膜糖蛋白（envelope glycoprotein, Env）三聚体BG505 SOSIP.v4.1-GT1.1，在多数疫苗接种者体内以较高频率诱导出了VRC01类广谱中和抗体前体细胞。这类靶向CD4受体结合位点的bnAb前体细胞，带有VRC01类抗体典型的体细胞超突变特征。研究中分离得到的部分VRC01类单克隆抗体可中和野生型假病毒，且其结构与经典bnAb VRC01极其相似。上述研究结果进一步为靶向生殖系策略用于人类HIV疫苗设计提供了支持，并证实通过理性疫苗设计可实现对B细胞应答的原子级精准操控。