Department of Clinical Laboratory, Chongqing General Hospital, Chongqing, China.
Department of Chemistry, Fudan University, Shanghai, China.
Front Immunol. 2022 Aug 24;13:956369. doi: 10.3389/fimmu.2022.956369. eCollection 2022.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings.
We performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information.
Significant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR).
The study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.
由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)造成了重大的生命和财产损失。针对这一严重的大流行,最近开发的 SARS-CoV-2 疫苗已向公众接种。然而,对 COVID-19 疫苗的人体免疫反应的研究还不够充分。尽管制药公司根据实验室研究和临床试验报告了与疫苗疗效、安全性和免疫原性相关的大量信息,但疫苗评估需要进一步扩展,以更好地了解 COVID-19 疫苗对人类的影响。
我们对 95 名参与者在接种科兴疫苗前后四个时间点采集的血清样本进行了比较肽组分析。采集的血清样本通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)进行分析,以描绘血清肽谱,并进行体液和细胞免疫反应分析,以获得典型的免疫原性信息。
接种后,MALDI-TOF MS 血清肽组图谱存在显著差异。通过有监督的统计分析,在接种后第 28 天和第 42 天共获得了 13 个血清 MALDI-TOF MS 特征峰。特征峰被鉴定为补体 C1q 受体、CD59 糖蛋白、甘露糖结合蛋白 C、血小板碱性蛋白、CD99 抗原、亮氨酸丰富的α-2-糖蛋白、整合膜蛋白 2B、血小板因子 4 和血红蛋白亚基。结合免疫原性分析,该研究为科兴疫苗激活的体液和细胞免疫反应提供了证据。此外,我们发现,使用 MALDI-TOF MS 血清肽谱结合机器学习方法(包括随机森林(RF)、偏最小二乘判别分析(PLS-DA)、线性支持向量机(SVM)和逻辑回归(LR)),有可能在完全接种疫苗后区分中和抗体(NAb)阳性和 NAb 阴性个体。
该研究表明,基于 MALDI-TOF MS 的血清肽组分析在评估 COVID-19 疫苗接种激活的免疫反应方面具有潜力,并发现了一组用于 COVID-19 疫苗接种和 NAb 产生的血清肽生物标志物。本研究中开发的方法不仅有助于新疫苗的开发,也有助于开发后疫苗的上市后评估。