Kuechler Anna Sabrina, Weinhold Sandra, Boege Fritz, Adams Ortwin, Müller Lisa, Babor Florian, Bennstein Sabrina B, Pham T-X Uyen, Hejazi Maryam, Reusing Sarah B, Hermsen Derik, Uhrberg Markus, Schulze-Bosse Karin
Central Institute for Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Vaccines (Basel). 2022 Jun 29;10(7):1044. doi: 10.3390/vaccines10071044.
Purpose: We describe a diagnostic procedure suitable for scheduling (re-)vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) according to individual state of humoral immunization. Methods: To clarify the relation between quantitative antibody measurements and humoral ex vivo immune responsiveness, we monitored 124 individuals before, during and six months after vaccination with Spikevax (Moderna, Cambridge, MA, USA). Antibodies against SARS-CoV-2 spike (S1) protein receptor-binding domain (S1-AB) and against nucleocapsid antigens were measured by chemiluminescent immunoassay (Roche). Virus-neutralizing activities were determined by surrogate assays (NeutraLISA, Euroimmune; cPass, GenScript). Neutralization of SARS-CoV-2 in cell culture (full virus NT) served as an ex vivo correlate for humoral immune responsiveness. Results: Vaccination responses varied considerably. Six months after the second vaccination, participants still positive for the full virus NT were safely determined by S1-AB levels ≥1000 U/mL. The full virus NT-positive fraction of participants with S1-AB levels <1000 U/mL was identified by virus-neutralizing activities >70% as determined by surrogate assays (NeutraLISA or cPas). Participants that were full virus NT-negative and presumably insufficiently protected could thus be identified by a sensitivity of >83% and a specificity of >95%. Conclusion: The described diagnostic strategy possibly supports individualized (re-)vaccination schedules based on simple and rapid measurement of serum-based SARS-CoV-2 antibody levels. Our data apply only to WUHAN-type SARS-CoV-2 virus and the current version of the mRNA vaccine from Moderna (Cambridge, MA, USA). Adaptation to other vaccines and more recent SARS-CoV-2 strains will require modification of cut-offs and re-evaluation of sensitivity/specificity.
我们描述了一种适用于根据个体体液免疫状态安排针对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的（重新）接种疫苗的诊断程序。方法：为了阐明定量抗体测量与体外体液免疫反应性之间的关系，我们在接种Spikevax（Moderna，美国马萨诸塞州剑桥）疫苗前、接种期间和接种后六个月对124名个体进行了监测。通过化学发光免疫分析（罗氏）测量针对SARS-CoV-2刺突（S1）蛋白受体结合域（S1-AB）和核衣壳抗原的抗体。通过替代试验（NeutraLISA，Euroimmune；cPass，金斯瑞）测定病毒中和活性。细胞培养中SARS-CoV-2的中和（全病毒中和试验）作为体液免疫反应性的体外相关指标。结果：疫苗接种反应差异很大。第二次接种后六个月，全病毒中和试验仍呈阳性的参与者通过S1-AB水平≥1000 U/mL得以安全确定。S1-AB水平<1000 U/mL的参与者中全病毒中和试验阳性部分通过替代试验（NeutraLISA或cPas）测定的病毒中和活性>70%得以确定。因此，全病毒中和试验阴性且可能保护不足的参与者可通过>83%的敏感性和>95%的特异性得以识别。结论：所描述的诊断策略可能支持基于简单快速测量血清中SARS-CoV-2抗体水平的个性化（重新）接种疫苗计划。我们的数据仅适用于武汉型SARS-CoV-2病毒和美国马萨诸塞州剑桥Moderna公司的当前版本mRNA疫苗。适应其他疫苗和更新的SARS-CoV-2毒株将需要调整临界值并重新评估敏感性/特异性。
