Wang Hongye, Yuan Ting, Li Tingting, Li Yanpeng, Qian Feng, Zhu Chuanwu, Liang Shujia, Hoffmann Daniel, Dittmer Ulf, Sun Binlian, Yang Rongge
Research Group of HIV-1 Molecular Epidemiology and Virology, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Arch Virol. 2018 Dec;163(12):3303-3315. doi: 10.1007/s00705-018-4011-7. Epub 2018 Sep 8.
Broadly neutralizing antibodies (bNAbs) are very promising agents for HIV-1 prophylaxis and AIDS treatment. However, the neutralization susceptibility of circulating recombinants such as CRF01_AE, which is becoming increasingly prevalent, has not been studied in detail until now. Here, we focused on CRF01_AE in China and aimed to find bNAbs that can be used for neutralization of CRF01_AE. Full-length env clones were obtained from the plasma samples of 22 HIV-1-infected individuals sampled in 2009 and 2015. An env-pseudovirus-based neutralization assay was conducted using five categories of bNAbs: VRC01, NIH45-46, and 3BNC117 (targeting the CD4 binding site); PG9 and PG16 (targeting the V1V2 loop); 2G12 (glycan specific), PGT121 and 10-1074 (targeting the V3 glycan); 2F5, 4E10, and 10E8 (targeting the membrane-proximal external region (MPER)). The neutralizing efficiency was compared, and features of the escape pseudoviruses were analyzed. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46 and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46and 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. Our results may help for choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
广谱中和抗体（bNAbs）是用于HIV-1预防和艾滋病治疗的非常有前景的药物。然而，直到现在，对如CRF01_AE这种日益流行的循环重组体的中和敏感性尚未进行详细研究。在此，我们聚焦于中国的CRF01_AE，并旨在找到可用于中和CRF01_AE的bNAbs。从2009年和2015年采集的22名HIV-1感染者的血浆样本中获得全长env克隆。使用五类bNAbs进行基于env假病毒的中和试验：VRC01、NIH45-46和3BNC117（靶向CD4结合位点）；PG9和PG16（靶向V1V2环）；2G12（聚糖特异性）、PGT121和10-1074（靶向V3聚糖）；2F5、4E10和10E8（靶向膜近端外部区域（MPER））。比较中和效率，并分析逃逸假病毒的特征。CRF01_AE假病毒对这些bNAbs表现出不同的敏感性。总体而言，4E10、10E8和3BNC117中和了所有22种env假型病毒，其次是NIH45-46和VRC01，它们中和了超过90%的病毒。2F5、PG9和PG16仅表现出中等广度，而其他三种bNAbs对这些假病毒均无中和作用。具体而言，10E8、NIH45-46和3BNC117显示出最高效率，兼具中和效力和广度。160、169、171位的突变与对PG9和PG16的抗性相关，而332位潜在聚糖的缺失导致对靶向V3聚糖[bNAbs]不敏感。我们的结果可能有助于在中国选择可优先用于预防或治疗方法中使用的bNAbs。
