Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals.

Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals.
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DOI:
10.1186/s12916-021-02055-9
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发表时间:
2021-07-26
期刊:
影响因子:
9.3
通讯作者:
Bradley T
Bradley T
中科院分区:
医学1区
文献类型:
--
作者:
Fraley E;LeMaster C;Geanes E;Banerjee D;Khanal S;Grundberg E;Selvarangan R;Bradley T

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2019冠状病毒病(COVID-19)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)技术的疫苗已显示出高疫苗效力。我们试图在有或没有自然SARS-CoV-2感染史的个体中,以高分辨率表征BNT162b2(辉瑞- biontech)疫苗免疫期间的体液免疫反应。研究人员在无SARS-CoV-2感染史(血清阴性)和首次接种前30-60天有病毒感染史(血清阳性)的个体中检测了每次接种BNT162b2 SARS-CoV-2疫苗后的抗体反应。为此,我们使用了针对多种SARS-CoV-2病毒蛋白抗原的抗体同型特异性多重头结合试验和确定潜在的SARS-CoV-2中和抗体水平的试验。此外,我们利用SARS-CoV-2刺突蛋白肽阵列绘制了免疫后抗体表位特异性。血清阳性个体单次注射后的抗体水平明显高于血清阴性个体,与血清阴性个体两次注射后的抗体水平相当。虽然血清阴性和血清阳性个体均可通过接种疫苗增强IgG,但只有血清阴性个体在初次免疫后才会增加IgA或IgM抗体滴度。我们鉴定了接种后靶向SARS-CoV-2刺突S1和S2亚基的免疫优势肽。这些发现证实了血清阳性和血清阴性个体对SARS-CoV-2免疫的抗体反应,并为使用既往感染史作为考虑未来疫苗接种方案的指导提供了支持。此外,我们确定了接种后抗体靶向的SARS-CoV-2刺突蛋白上的关键表位,可以指导未来疫苗和免疫相关的开发。在线版本包含补充材料,可在10.1186/s12916-021-02055-9获得。
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. The online version contains supplementary material available at 10.1186/s12916-021-02055-9.
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发表时间: 2019-11-01
影响因子: 15.9
作者:
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影响因子: 82.9
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影响因子: 8.8
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