After nearly four decades of research, a safe and effective HIV-1 vaccine remains elusive. There are many reasons why the development of a potent and durable HIV-1 vaccine is challenging, including the extraordinary genetic diversity of HIV-1 and its complex mechanisms of immune evasion. HIV-1 envelope glycoproteins are poorly recognized by the immune system, which means that potent broadly neutralizing antibodies (bnAbs) are only infrequently induced in the setting of HIV-1 infection or through vaccination. Thus, the biology of HIV-1–host interactions necessitates novel strategies for vaccine development to be designed to activate and expand rare bnAb-producing B cell lineages and to select for the acquisition of critical improbable bnAb mutations. Here we discuss strategies for the induction of potent and broad HIV-1 bnAbs and outline the steps that may be necessary for ultimate success.

经过近四十年的研究，安全有效的 HIV-1 疫苗仍然难以实现。开发有效且持久的 HIV-1 疫苗具有挑战性的原因有很多，其中包括 HIV-1 非凡的遗传多样性及其复杂的免疫逃避机制。 HIV-1 包膜糖蛋白很难被免疫系统识别，这意味着在 HIV-1 感染或通过疫苗接种时很少会诱导出有效的广泛中和抗体 (bnAb)。因此，HIV-1-宿主相互作用的生物学需要设计新的疫苗开发策略来激活和扩展罕见的产生 bnAb 的 B 细胞谱系，并选择获得关键的不可能的 bnAb 突变。在这里，我们讨论了诱导有效且广泛的 HIV-1 bnAb 的策略，并概述了最终成功可能必要的步骤。