Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage–designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41—named “SOS”—and an isoleucine-to-proline point mutation—named “IP”—at residue 559) to induce precursor CD4 binding site (CD4bs)–targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line–targeting BG505 SOSIP GT1.1 ( n = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants ( n = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage–designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.

中文翻译：

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使用针对种系的 SOSIP 三聚体进行免疫可在幼年猕猴中引发广泛中和抗体前体


青少年是艾滋病毒感染者中不断增长的群体。断奶和初次性行为之间的这段时期是感染艾滋病毒的低风险窗口，使幼儿期成为实施免疫接种方案的理想时期。由于广泛中和抗体 (bnAb) 的引发对于有效的 HIV 疫苗至关重要，因此我们的目标是评估 bnAb B 细胞谱系设计的 HIV 包膜 SOSIP（由 gp120-gp41 之间的二硫键稳定的蛋白质，名为“ SOS”——以及名为“IP”的异亮氨酸至脯氨酸点突变（位于残基 559），以诱导前体 CD4 结合位点 (CD4bs)——在生命早期靶向 bnAb。幼年恒河猴接受基于婴儿 BG505 传播/创始人病毒的 BG505 SOSIP，或针对 BG505 SOSIP GT1.1 的 CD4bs 种系（每组 n = 5）。尽管这两种策略都能诱导持久、高强度的血浆自体病毒中和反应，但只有 GT1.1 免疫的婴儿（n = 3 of 5）表现出 VRC01 样 CD4bs bnAb 前体发育。因此，采用 bnAb 谱系设计的 SOSIP 的多剂量免疫方案有望诱导早期 B 细胞反应，并有可能在首次性行为前成熟为保护性 HIV bnAb。