Laboratory of Molecular Immunology, The Rockefeller University, New York, United States.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Elife. 2020 Oct 21;9:e61991. doi: 10.7554/eLife.61991.
A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.
一小部分感染 HIV-1 的人类会产生针对 HIV-1 的广泛中和抗体 (bNAbs)，这些抗体可以保护猕猴免受嵌合猴免疫缺陷病毒 (SHIV) 的侵害。同样，少数感染 SHIV 的猕猴也会产生广泛中和的血清学活性，但对猿类抗体的性质知之甚少。在这里，我们报告了一种从感染了 SHIVAD8 的猕猴中分离出来的单克隆抗体 Ab1485，该抗体针对 HIV-1 Env 的 V3-聚糖区域产生了广泛中和的血清学活性。Ab1485 在 42 个假病毒面板中中和了 38.1%的 HIV-1 分离株，几何平均 IC50 为 0.055 µg/mLl，中和 SHIVAD8 的 IC50 为 0.028 µg/mLl。Ab1485 以糖依赖性方式结合 V3-聚糖表位。Ab1485 与天然样 SOSIP Env 三聚体复合物的 3.5 Å 冷冻电镜结构显示与 N332gp120 聚糖和 gp120 GDIR 肽基序保守接触，但相对于人类 V3/N332gp120 聚糖靶向 bNAbs 具有不同的 Env 结合取向。Ab1485 的静脉内输注可保护猕猴免受高剂量 SHIVAD8 的攻击。我们得出结论，猕猴可以产生针对 V3-聚糖斑块的 bNAbs，类似于人类 V3-聚糖 bNAbs。
