SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.

SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.
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DOI:
10.1128/mbio.02940-20
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发表时间:
2021-01-19
期刊:
影响因子:
6.4
通讯作者:
Wilson PC
Wilson PC
中科院分区:
生物学1区
文献类型:
--
作者:
Guthmiller JJ;Stovicek O;Wang J;Changrob S;Li L;Halfmann P;Zheng NY;Utset H;Stamper CT;Dugan HL;Miller WD;Huang M;Dai YN;Nelson CA;Hall PD;Jansen M;Shanmugarajah K;Donington JS;Krammer F;Fremont DH;Joachimiak A;Kawaoka Y;Tesic V;Madariaga ML;Wilson PC

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随着疫情的持续,了解针对SARS-CoV-2和新冠肺炎的自然免疫力是如何发展的至关重要。我们已经确定,患有更严重的新冠肺炎病的受试者对SARS-CoV-2刺突蛋白的抗体反应更强劲和中和。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)目前正在引起一场全球大流行。针对这种新病毒的抗体反应的抗原特异性还没有被详细了解。在这里,我们报告了SARS-CoV-2感染越严重的受试者对尖峰蛋白和核衣壳蛋白的抗体反应越强,并对次要病毒抗原(如开放阅读框架8和非结构蛋白)的表位扩散。抗体反应较强的受试者对尖峰蛋白的记忆B细胞反应较大,但对核衣壳蛋白的反应不大。此外,我们还发现抗S蛋白的抗体仍然能够与D614G S蛋白突变体结合,并与SARS-CoV-1受体结合域发生交叉反应。总而言之,这项研究表明,SARS-CoV-2感染越严重的受试者,对尖峰和核衣壳蛋白的总体抗体反应越强,对尖峰的记忆B细胞反应也越大。
With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.