An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%–77% breadth (geometric mean 50% inhibitory dilution [ID₅₀] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%–60% (50% inhibitory concentration [IC₅₀] < 50 μg/mL) and total lineage-concentrations estimates of 50–200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.

中文翻译：

---

在融合肽引发的 SHIV 感染的猕猴中有效且广泛的 HIV-1 中和


基于抗体的 HIV-1 疫苗需要诱导有效的交叉反应性 HIV-1 中和反应。为了证明实现这一目标的可行性，我们将针对易感性融合肽位点的疫苗接种与猿猴-人类免疫缺陷病毒 （SHIV） 感染相结合。在四只具有疫苗诱导的中和反应的猕猴中，SHIV 感染在 208 株面板上将血浆中和提高到 45%-77% 宽度（几何平均 50% 抑制稀释 [ID₅₀] ∼100）。通过抗体分离和冷冻电子显微镜 （cryo-EM） 结构测定对这些反应进行分子解剖，发现 16 个抗体谱系中有 15 个具有交叉分支中和作用，指向易损的融合肽位点。在每只猕猴中，从记忆 B 细胞中分离的抗体概括了血浆中和反应，融合肽结合抗体的宽度达到 40%–60%（50% 抑制浓度 [IC₅₀] < 50 μg/mL），总谱系浓度估计值为 50–200 μg/mL。纵向标测表明，这些反应发生在 SHIV 感染之前。总的来说，这些结果为一到几个 B 细胞谱系提供了 体内分子示例，这些谱系提供了有效的、广泛的中和血浆反应。