ABSTRACT

Recent studies have shown the potential of broadly neutralizing antibodies (bnAbs) for HIV-1 treatment. One of the candidate antibodies moving into clinical trials is the bnAb PGDM1400. Here, we studied the therapeutic potency and escape pathways of bnAb PGDM1400 during monovalent therapy in human immune system (HIS) mice using the BG505, REJO, MJ4 and AMC008 virus isolates. PGDM1400 administered during chronic infection caused a modest decrease in viral load in the first week of administration in 7 out of 10 animals, which correlated with the in vitro neutralization sensitivity of the viruses to PGDM1400. As expected for monotherapy, viral loads rebounded after about a week and different viral escape pathways were observed, involving the deletion of glycans in the envelope glycoprotein at positions 130 or 160. (Pre)clinical trials should reveal whether PGDM1400 is a useful component of an antibody combination treatment or as part of a tri-specific antibody.

摘要

最近的研究表明，广泛中和抗体（bnAbs）的潜力用于HIV-1治疗。进入临床试验的候选抗体之一是bnAb PGDM1400。在这里，我们研究了使用BG505，REJO，MJ4和AMC008病毒分离株在人免疫系统（HIS）小鼠中单价治疗期间bnAb PGDM1400的治疗效力和逃逸途径。在慢性感染期间施用的PGDM1400在施用的第一周内导致10只动物中的7只病毒载量适度降低，这与体外相关病毒对PGDM1400的中和敏感性。正如单药疗法所预期的那样，大约一周后病毒载量反弹，并且观察到不同的病毒逃逸途径，涉及在第130或160位的包膜糖蛋白中的聚糖缺失。抗体组合治疗或作为三特异性抗体的一部分。