Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5–amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)–specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

人类抗 HIV-1 广泛中和抗体 (bNAb) 可在动物模型中防止感染。然而，在多种野生型动物或人类中，疫苗接种尚未引发 bNAb，部分原因是表达这些抗体前体的 B 细胞无法识别大多数 HIV-1 包膜 (Env)。免疫原被设计用于在体内激活这些 B 细胞前体，但它们也会激活竞争性脱靶反应。在这里，我们报告了一种使用抗独特型抗体 iv8 扩增特定 B 细胞的互补方法，该方法选择表达具有 5 个氨基酸互补决定区 3s 的免疫球蛋白轻链的初始人类 B 细胞，这是抗 CD4 结合的关键特征位点 (CD4bs) – 特异性 VRC01 类抗体。在小鼠中，iv8 在多克隆免疫系统的背景下诱导靶细胞扩增和成熟，并产生针对 Env 上 CD4b 的血清学反应。总之，结果表明，抗独特型抗体可以特异性识别并扩增表达针对 HIV-1 的 VRC01 类抗体的稀有 B 细胞。