Next-generation Serology by Mass Spectrometry:Readout of the SARS-CoV-2 Antibody Repertoire

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses new advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and degree of clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.

抗体检测方法常用于评估个体对病原体的暴露情况或免疫状态。本研究提出一种全新的血清学检测技术Ig-MS，可在分子分辨率下完整捕获免疫球蛋白（Ig）库，涵盖免疫球蛋白轻链与重链的全部可变区域。Ig-MS依托蛋白质质谱（MS）领域的最新进展，实现抗体的多参数检测，其创新性指标包括离子滴度（IT）与克隆性程度（DoC），无需对B细胞（B cells）进行测序即可精准反映单个克隆的异质性与相对丰度。我们将Ig-MS应用于重症与轻症新型冠状病毒肺炎（COVID-19）受试者的血浆样本，以严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的受体结合域（RBD）作为抗体捕获的诱饵。值得注意的是，本研究首次报道了一种适用于人类血清学研究的新型数据类型，该方法可兼容任意重组抗原，用以评估机体针对疫苗接种、病原体感染或自身免疫疾病的免疫应答。