Despite enormous efforts no HIV-1 vaccine has been developed that elicits broadly neutralizing antibodies (bNAbs) to protect against infection to date. The high antigenic diversity and dense N-linked glycan armor, which covers nearly the entire HIV-1 envelope protein (Env), are major roadblocks for the development of bNAbs by vaccination. In addition, the naive human antibody repertoire features a low frequency of exceptionally long heavy chain complementary determining regions (CDRH3s), which is a typical characteristic that many HIV-1 bNAbs use to penetrate the glycan armor. Native-like Env trimer immunogens can induce potent but strain-specific neutralizing antibody responses in animal models but how to overcome the many obstacles towards the development of bNAbs remains a challenge. Here, we review recent HIV-1 Env immunization studies and discuss strategies to guide strain-specific antibody responses towards neutralization breadth.

中文翻译：

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HIV-1 免疫原和驱动抗体反应向中和广度方向发展的策略

尽管付出了巨大的努力，但迄今为止，仍未开发出能引发广泛中和抗体 (bNAb) 以防止感染的 HIV-1 疫苗。高抗原多样性和密集的 N 连接聚糖盔甲几乎覆盖了整个 HIV-1 包膜蛋白 (Env)，是通过疫苗接种开发 bNAb 的主要障碍。此外，初始人类抗体库的特点是频率异常长的重链互补决定区 (CDRH3)，这是许多 HIV-1 bNAb 用于穿透聚糖装甲的典型特征。天然样 Env 三聚体免疫原可以在动物模型中诱导有效但菌株特异性的中和抗体反应，但如何克服发展 bNAb 的许多障碍仍然是一个挑战。这里，