St Germain Russell, Bossard Emily L, Corey Lawrence, Sholukh Anton M
Vaccine and Infectious Diseases Division, Fred Hutch Cancer Research Center, Seattle, WA 98109, USA.
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
iScience. 2023 Aug 3;26(9):107527. doi: 10.1016/j.isci.2023.107527. eCollection 2023 Sep 15.
Because virus neutralization cannot solely explain vaccine-induced, antibody-mediated protection, antibody effector functions are being considered as a potential correlate of protection (CoP). However, measuring effector functions at a fixed serum dilution for high throughput purposes makes it difficult to distinguish between the effect of serum antibody concentration and antibody properties such as epitopes, subclass, and glycosylation. To address this issue, we evaluated antibody-dependent cellular phagocytosis (ADCP) assay against SARS-CoV-2 spike. Adjustment of serum samples to the same concentration of antigen-specific IgG prior to the ADCP assay revealed concentration-independent differences in ADCP after mRNA vaccination in subjects with and without prior SARS-CoV-2 infection not detectable in assay performed with fixed serum dilution. Phagocytosis measured at different concentrations of spike-specific IgG strongly correlated with the area under the curve (AUC) indicating that ADCP assay can be performed at a standardized antibody concentration for the high throughput necessary for vaccine trial analyses.
由于病毒中和作用不能完全解释疫苗诱导的、抗体介导的保护作用，抗体效应功能正被视为一种潜在的保护相关性指标（CoP）。然而，为了高通量目的在固定血清稀释度下测量效应功能，很难区分血清抗体浓度的影响与抗体特性（如表位、亚类和糖基化）的影响。为了解决这个问题，我们评估了针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的抗体依赖性细胞吞噬作用（ADCP）检测方法。在ADCP检测之前将血清样本调整到相同浓度的抗原特异性免疫球蛋白G（IgG），发现在有和没有既往SARS-CoV-2感染的受试者中，mRNA疫苗接种后ADCP存在与浓度无关的差异，而在固定血清稀释度的检测中未检测到这种差异。在不同浓度的刺突特异性IgG下测量的吞噬作用与曲线下面积（AUC）密切相关，这表明ADCP检测可以在标准化抗体浓度下进行，以满足疫苗试验分析所需的高通量要求。
