The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays. Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination. These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

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血清阳性和血清阴性个体在 SARS-CoV-2 mRNA 疫苗接种期间的体液免疫反应

2019 年冠状病毒病 (COVID-19) 的全球大流行是由感染 SARS-CoV-2 病毒引起的。目前，美国批准了三种针对 SARS-CoV-2 的疫苗，其中两种基于信使 RNA (mRNA) 技术，已显示出很高的疫苗效力。我们试图在有或没有自然 SARS-CoV-2 感染史的个体中使用 BNT162b2 (Pfizer-BioNTech) 疫苗进行免疫期间，以高分辨率表征体液免疫反应。我们在没有 SARS-CoV-2 感染史的个体（血清阴性）和在首次接种疫苗前 30-60 天曾感染过病毒的个体（血清阳性）。去做这个，我们使用了针对多种 SARS-CoV-2 病毒蛋白抗原的抗体同种型特异性多重基于珠子的结合测定，以及一种确定潜在 SARS-CoV-2 中和抗体水平的测定。此外，我们使用 SARS-CoV-2 刺突蛋白肽阵列在免疫后绘制了抗体表位特异性。与血清阴性个体相比，血清阳性个体单次给药后的抗体水平显着更高，并且与两次给药后血清阴性个体中观察到的水平相当。虽然 IgG 通过对血清阴性和血清阳性个体进行疫苗接种而得到加强，但只有血清阴性个体在初次免疫后 IgA 或 IgM 抗体滴度增加。我们确定了疫苗接种后针对 SARS-CoV-2 尖峰 S1 和 S2 亚基的免疫优势肽。这些发现证明了血清阳性和血清阴性个体对 SARS-CoV-2 免疫接种的抗体反应，并为使用既往感染史作为考虑未来疫苗接种方案的指南的概念提供了支持。此外，我们确定了 SARS-CoV-2 刺突蛋白上的关键表位，这些表位在疫苗接种后被抗体靶向，可以指导未来的疫苗和免疫相关发展。