The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Front Immunol. 2022 Aug 9;13:938378. doi: 10.3389/fimmu.2022.938378. eCollection 2022.
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected millions of people around the world. Vaccination is a pillar in the strategy to control transmission of the SARS-CoV-2 spread. Immune responses to vaccination require elucidation.
The immune responses to vaccination with three doses of inactivated SARS-CoV-2 vaccine were followed in a cohort of 37 healthy adults (18-59 years old). Blood samples were collected at multiple time points and submitted to peptide array, machine learning modeling, and sequence alignment analyses, the results of which were used to generate vaccine-induced antibody-binding region (VIABR) immunosignatures (Registration number: ChiCTR2200058571).
Antibody spectrum signals showed vaccination stimulated antibody production. Sequence alignment analyses revealed that a third vaccine dose generated a new highly represented VIABR near the A570D mutation, and the whole process of inoculation enhanced the VIABR near the N501Y mutation. In addition, the antigen conformational epitopes varied between short- and long-term samples. The amino acids with the highest scores in the short-term samples were distributed primarily in the receptor binding domain (RBD) and N-terminal domain regions of spike (S) protein, while in the long-term samples (12 weeks after the 2 dose), some new conformational epitopes (CEs) were localized to crevices within the head of the S protein trimer.
Protective antigenic epitopes were revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine inoculation. A third dose results in a new top-10 VIABR near the A570D mutation site of S protein, and the whole process of inoculation enhanced the VIABR near the N501Y mutation, thus potentially providing protection from strains that have gained invasion and immune escape abilities through these mutation.
SARS-CoV-2（严重急性呼吸综合征冠状病毒 2）已在全球范围内感染了数百万人。疫苗接种是控制 SARS-CoV-2 传播的策略的重要组成部分。需要阐明对疫苗接种的免疫反应。
对 37 名健康成年人（18-59 岁）进行了三剂灭活 SARS-CoV-2 疫苗接种的免疫反应随访。在多个时间点采集血样，并进行肽阵列、机器学习建模和序列比对分析，分析结果用于生成疫苗诱导的抗体结合区（VIABR）免疫特征（注册号：ChiCTR2200058571）。
抗体谱信号表明疫苗接种刺激了抗体产生。序列比对分析显示，第三剂疫苗接种在 A570D 突变附近产生了一个新的高代表性 VIABR，整个接种过程增强了 N501Y 突变附近的 VIABR。此外，抗原构象表位在短期和长期样本之间存在差异。短期样本中得分最高的氨基酸主要分布在刺突（S）蛋白的受体结合域（RBD）和 N 端结构域区域，而在长期样本（接种 2 剂后 12 周）中，一些新的构象表位（CEs）定位于 S 蛋白三聚体头部的缝隙中。
三剂灭活 SARS-CoV-2 疫苗接种后，通过免疫特征揭示了保护性抗原表位。第三剂疫苗接种导致 S 蛋白 A570D 突变位点附近出现新的排名前 10 的 VIABR，整个接种过程增强了 N501Y 突变附近的 VIABR，从而可能为通过这些突变获得入侵和免疫逃逸能力的菌株提供保护。
