Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Nat Commun. 2023 Jun 17;14(1):3605. doi: 10.1038/s41467-023-39292-w.
While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs.
虽然针对 SARS-CoV-2 的新型疫苗是基于针对新出现的关注变异株的中和抗体 (nAb) 滴度获得授权的，但预防用单克隆抗体 (mAb) 却没有类似的途径。在这项工作中，nAb 滴度被评估为 casirivimab + imdevimab 单克隆抗体 (mAb) 预防试验 (ClinicalTrials.gov #NCT4452318) 和 mRNA-1273 疫苗试验 (ClinicalTrials.gov #NCT4470427) 中预防 COVID-19 的保护相关性。在 mAb 试验中，92% (95%置信区间 (CI): 84%, 98%) 的保护效力与 1000 IU50/ml 的 nAb 滴度相关，而较低的 nAb 滴度则效力较低。在疫苗试验中，93% [95% CI: 91%, 95%] 和 97% (95% CI: 95%, 98%) 的保护效力分别与 100 和 1000 IU50/ml 的 nAb 滴度相关。这些数据定量了 mAb 保护的 nAb 滴度相关性，该相关性与疫苗诱导的 nAb 滴度相媲美，并支持 nAb 滴度作为授权新 mAb 的替代终点。
