Department of Pediatrics, Maternal, Child and Adolescent Center for Infectious Diseases and Virology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.
Microbiol Spectr. 2023 Feb 14;11(1):e0370922. doi: 10.1128/spectrum.03709-22. Epub 2023 Jan 23.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody (Ab) levels following vaccination or natural infection could be used as a surrogate for immune protection if results of serological assays were standardized to yield quantitative results using an international standard. Using a bead-based serological assay (Luminex xMAP), anti-receptor binding domain (anti-RBD) Ab levels were determined for 1,450 participants enrolled in the Los Angeles Pandemic Surveillance Cohort (LAPSC) study. For 123 participants, SARS-CoV-2 binding antibody unit (BAU) levels were also quantified using WHO standards and then compared to the semiquantitative results. Samples were chosen to represent the range of results and time from vaccination. Antibody levels and decay rates were then compared using unadjusted and adjusted linear regression models. The linear range of the assay used in this study was determined to be 300 to 5,000 mean fluorescence intensity units (MFI). Among the fully vaccinated groups (vaccinated only and vaccinated with past infection), 84.8% had anti-RBD MFI values above the linear range of >5,000 MFI, and 33.8% had values of >15,000 MFI. Among vaccinated participants with past infection (hybrid immunity), 97% had anti-RBD values of >5,000 MFI and 70% (120/171) had anti-RBD values of >15,000 MFI. In the subgroup quantified using the WHO control, BAU levels were significantly higher than the semiquantitative MFI results. In vaccinated participants, Ab decay levels were similar between infected and noninfected groups ( = 0.337). These results demonstrate that accurate quantitation is possible if standardized with an international standard. BAU can then be compared over time or between subjects and would be useful in clinical decision making. Accurate quantification of SARS-CoV-2-specific antibodies can be achieved using a universal standard with sample dilution within the linear range. With hybrid immunity being now common, it is critical to use protocols adapted to high Ab levels to standardize serological results. We validated this approach with the Los Angeles Pandemic Surveillance Cohort by comparing the antibody decay rates in vaccinated participants and vaccinated infected participants.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 结合抗体 (Ab) 水平可作为免疫保护的替代指标，如果使用国际标准对血清学检测结果进行标准化以产生定量结果，则可用于接种疫苗或自然感染后。使用基于珠的血清学检测 (Luminex xMAP)，对洛杉矶大流行监测队列 (LAPSC) 研究中招募的 1450 名参与者的抗受体结合域 (anti-RBD) Ab 水平进行了测定。对于 123 名参与者，还使用世界卫生组织 (WHO) 标准对 SARS-CoV-2 结合抗体单位 (BAU) 水平进行了定量，然后将其与半定量结果进行了比较。选择样本以代表结果和接种疫苗后的时间范围。然后使用未调整和调整后的线性回归模型比较抗体水平和衰减率。本研究中使用的检测线性范围确定为 300 至 5,000 平均荧光强度单位 (MFI)。在完全接种疫苗组(仅接种疫苗和接种疫苗合并既往感染)中，84.8%的抗-RBD MFI 值高于>5,000 MFI 的线性范围，33.8%的抗-RBD MFI 值高于>15,000 MFI。在既往感染的接种疫苗参与者(混合免疫)中，97%的抗-RBD 值高于>5,000 MFI，70% (120/171) 的抗-RBD 值高于>15,000 MFI。在使用世界卫生组织对照进行量化的亚组中，BAU 水平明显高于半定量 MFI 结果。在接种疫苗的参与者中，感染组和未感染组的 Ab 衰减水平相似(=0.337)。这些结果表明，如果使用国际标准进行标准化，则可以进行准确的定量。BAU 可以随时间或在不同对象之间进行比较，这在临床决策中很有用。使用具有线性范围内样本稀释的通用标准可以实现对 SARS-CoV-2 特异性抗体的准确定量。由于混合免疫现在很常见，因此必须使用适应高 Ab 水平的方案来标准化血清学结果。我们通过比较接种疫苗的参与者和接种疫苗合并感染的参与者的抗体衰减率，用洛杉矶大流行监测队列验证了这种方法。
