University of Pennsylvania.
The Wistar Institute, Philadelphia, PA.
AIDS. 2023 Jul 1;37(8):1203-1207. doi: 10.1097/QAD.0000000000003575. Epub 2023 Apr 11.
The aim of this study was to assess the susceptibility of HIV to two HIV monoclonal antibodies (bnAbs), 3BNC117 and 10-1074, in individuals with chronically antiretroviral therapy (ART) suppressed HIV infection.
The susceptibility of bnAbs was determined using the PhenoSense mAb Assay, which is a cell-based infectivity assay designed to assess the susceptibility of luciferase-reporter pseudovirions. This assay is the only Clinical Laboratory Improvement Ammendment (CLIA)/College of American Pathologist (CAP) compliant screening test specifically developed for evaluating bnAb susceptibility in people with HIV infection.
The susceptibility of luciferase-reporter pseudovirions, derived from HIV-1 envelope proteins obtained from peripheral bloodmononuclear cells of 61 ART-suppressed individuals, to 3BNC117 and 10-1074 bnAbs was assessed using the PhenoSense mAb assay. Susceptibility was defined as an IC 90 of <2.0 μg/ml and 1.5 μg/ml for 3BNC117 and 10-1074, respectively.
About half of the individuals who were chronically infected and virologically suppressed were found to harbor virus with reduced susceptibility to one or both of the tested bnAbs.
The reduced combined susceptibility of 3BNC117 and 10-1074 highlights a potential limitation of using only two bnAbs for pre-exposure prophylaxis or treatment. Further studies are needed to define and validate the clinical correlates of bnAb susceptibility.
本研究旨在评估两种 HIV 单克隆抗体（bnAb），即 3BNC117 和 10-1074，在慢性抗逆转录病毒治疗（ART）抑制 HIV 感染个体中的敏感性。
使用 PhenoSense mAb 测定法来确定 bnAb 的敏感性，该测定法是一种基于细胞的感染性测定法，旨在评估报告荧光素酶的假病毒对 HIV 的敏感性。该测定法是唯一经过临床实验室改进修正案（CLIA）/美国病理学家学会（CAP）认证的筛选检测方法，专门用于评估 HIV 感染者中 bnAb 的敏感性。
使用 PhenoSense mAb 测定法评估来自 61 名慢性 ART 抑制个体外周血单个核细胞中 HIV-1 包膜蛋白的报告荧光素酶假病毒对 3BNC117 和 10-1074 bnAb 的敏感性。将敏感性定义为对 3BNC117 和 10-1074 的 IC90 分别<2.0μg/ml 和 1.5μg/ml。
约一半的慢性感染和病毒学抑制的个体被发现携带对一种或两种测试的 bnAb 敏感性降低的病毒。
3BNC117 和 10-1074 的联合敏感性降低突出了仅使用两种 bnAb 进行暴露前预防或治疗的潜在局限性。需要进一步研究来定义和验证 bnAb 敏感性的临床相关性。
