Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands.
Center for Translational Immunology, University Medical Centre Utrecht, the Netherlands.
J Infect Dis. 2024 Jul 25;230(1):e93-e101. doi: 10.1093/infdis/jiad543.
The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAbs) is virus neutralization, measured via sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials and thereby reduce costs. In this study, we validate an assay to measure RSV neutralization in dried capillary blood.
Functional antibodies were compared between matched serum and dried blood samples from a phase 1 trial with RSM01, an investigational anti-RSV prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture by using RSV-A2-mKate to determine the half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress.
Functional antibodies in dried blood were highly correlated with serum (R2 = 0.98, P < .0001). The precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples.
We demonstrated the feasibility of measuring RSV neutralization using dried blood as a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2. Clinical Trials Registration. NCT05118386 (ClinicalTrials.gov).
呼吸道合胞病毒（RSV）疫苗和单克隆抗体（mAbs）的关键保护相关因素是病毒中和作用，通过静脉穿刺获得的血清进行测量。使用手指采血获得的干血斑可以简化试验中的采集、处理、储存和运输，从而降低成本。在这项研究中，我们验证了一种用于测量干血斑中 RSV 中和作用的检测方法。
在一项评估 RSM01（一种研究性抗 RSV 预融合 F mAb）的 1 期临床试验中，我们比较了匹配血清和干血斑样本中的功能性抗体。使用 RSV-A2-mKate 对 Hep-2 细胞进行病毒滴度感染，以确定半最大抑制浓度。我们还评估了干血斑随时间和温度应激的稳定性。
干血斑中的功能性抗体与血清高度相关（R2 = 0.98，P <.0001）。干血斑检测的精密度与血清相似。在室温下，mAb 的功能可稳定保存 9 个月，冻干血斑样本也具有稳定性。
我们证明了使用干血斑测量 RSV 中和作用的可行性，这是一种以患者为中心的解决方案，可能会替代 RSV 或其他病毒（如流感和 SARS-CoV-2）试验中的血清学检测。临床试验注册。NCT05118386（ClinicalTrials.gov）。
