An effective HIV vaccine must induce broadly neutralizing antibodies (bnAbs) that target the most conserved sites of the HIV envelope, a feat that has not yet been achieved in humans. Germline-targeting vaccine design holds promise by using immunogens to prime naive B cells for bnAb precursor activation and then boosting their maturation. A major challenge for this approach is that antibody–antigen recognition depends on a long heavy chain complementarity determining region 3 (HCDR3) loop on naive B cells, which is present at very low frequencies. Two papers in Science describe an immunization strategy that effectively primes and boosts maturation of B cell precursors to produce the HCDR3-dominant bnAb BG18.

In the first study, Steichen et al. used the priming immunogen N332-GT5 to target BG18 precursors in rhesus macaques. Immunization with N332-GT5 and adjuvant saponin/MPLA nanoparticles reliably induced diverse BG18-class precursors in all eight animals. Structural analysis confirmed the binding of antibodies with BG18-class HCDR3s to HIV trimer glycoproteins, similar to BG18.

有效的 HIV 疫苗必须诱导针对 HIV 包膜最保守位点的广泛中和抗体 (bnAb)，这一壮举尚未在人类身上实现。种系靶向疫苗设计有望通过使用免疫原来启动幼稚 B 细胞以激活 bnAb 前体，然后促进其成熟。这种方法的一个主要挑战是抗体-抗原识别依赖于初始 B 细胞上的长重链互补决定区 3 (HCDR3) 环，而该环的出现频率非常低。 《科学》杂志上的两篇论文描述了一种免疫策略，该策略可有效启动和促进 B 细胞前体成熟，以产生 HCDR3 主导的 bnAb BG18。

在第一项研究中，Steichen 等人。使用引发免疫原 N332-GT5 来靶向恒河猴中的 BG18 前体。使用 N332-GT5 和佐剂皂苷/MPLA 纳米颗粒进行的免疫确实在所有八只动物中诱导了不同的 BG18 类前体。结构分析证实了带有 BG18 类 HCDR3 的抗体与 HIV 三聚体糖蛋白的结合，类似于 BG18。