Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
National Medical Products Administration (NMPA) Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Guangzhou, China.
Front Immunol. 2021 Nov 19;12:772511. doi: 10.3389/fimmu.2021.772511. eCollection 2021.
Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% 12.0% ± 2.2%, =0.990) and post-vaccination (43.8% ± 25.1% 44.6% ± 21.5%, =0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.
最近接触季节性冠状病毒（sCoV）可能会刺激针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的交叉反应性抗体反应。然而，先前的研究对于先前 sCoV 暴露诱导的保护性或破坏性免疫产生了不同的结果。目前尚不清楚先前存在的体液免疫是否在疫苗诱导的中和和抗体反应中发挥作用。在这项研究中，我们从 36 名接受过灭活全病毒 SARS-CoV-2 疫苗接种的健康志愿者中收集了 36 对血清样本，在接种疫苗之前分析了表位水平上预先存在的抗体反应的分布和强度，以及预先存在的 sCoV 免疫与疫苗诱导的中和之间的关系。我们观察到在 sCoV 之间保守区域存在大量的预先存在的交叉反应性抗体，特别是 S2 亚基。除了少数几个肽段外，在接受两剂 COVID-19 疫苗后中和抑制率（%抑制）<40 和%抑制≥40 的疫苗接种者的预接种和接种后血清中，S、M 和 N 肽的 IgG 和 IgM 荧光强度没有显著差异。具有强和弱预先存在的交叉反应性抗体（强预-CRA；弱预-CRA）的参与者在预接种时具有相似的%抑制（10.9%±2.9% 12.0%±2.2%，=0.990）和接种后（43.8%±25.1% 44.6%±21.5%，=0.997）。总体而言，与弱预-CRA 组相比，强预-CRA 组在接种后对 S 蛋白线性肽的抗体反应没有显著增加。因此，我们没有发现预先存在的抗体反应对灭活疫苗诱导的中和和抗体反应有显著影响的证据。我们的研究为高 sCoV 血清阳性率背景下使用灭活 SARS-CoV-2 疫苗提供了重要依据。
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