Background Development of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives. Methods We assessed the PhenoSense Monoclonal Antibody Assay (Labcorp-Monogram Biosciences), which is Clinical Laboratory Improvement Amendments (CLIA) validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials. Results When performed on plasma and longitudinal peripheral blood mononuclear cell samples (before and during antiretroviral therapy, respectively), as sourced from a recent clinical trial, the PhenoSense assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. When applied retrospectively to baseline samples from 3 recent studies, the PhenoSense assay correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of assay feasibility in 4 recent clinical studies provides estimates of assay success rate and processing time. Conclusions The PhenoSense Monoclonal Antibody Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet is not consistently predictive of virus suppression. Logistical and operational assay requirements can affect timely clinical trial conduct. These results inform bnAb studies in development.

中文翻译：

---

用于广泛中和抗 HIV-1 抗体的中和敏感性筛选测定的评估和实际经验


背景 开发用于临床使用广泛中和抗体 （bnAbs） 的筛查测定是 HIV 治疗和治愈计划的优先事项。方法 我们评估了 PhenoSense 单克隆抗体检测 （Labcorp-Monogram Biosciences），该检测已通过临床实验室改进修正案 （CLIA） 验证，并已在最近的多项 bnAb 临床试验中前瞻性和回顾性使用。结果当对血浆和纵向外周血单核细胞样本进行时（分别为抗逆转录病毒治疗前和治疗期间），根据最近的一项临床试验，PhenoSense 检测产生了强大的重现性、样本类型之间的一致性以及临床开发中 bnAbs 敏感性测量的预期范围。当回顾性应用于最近 3 项研究的基线样本时，PhenoSense 测定与已发表的基于实验室的研究评估相关，但基线 bnAb 易感性并不能始终预测持久的病毒抑制。最近 4 项临床研究中的检测可行性评估提供了检测成功率和处理时间的估计值。结论 PhenoSense 单克隆抗体检测可在相关样品类型中提供可重现的 bnAb 敏感性测量，但不能一致地预测病毒抑制。后勤和运营检测要求会影响临床试验的及时进行。这些结果为正在开发的 bnAb 研究提供了信息。