Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection.

Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection.
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DOI:
10.3389/fimmu.2022.901217
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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--
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在许多病毒中都观察到fc介导的病毒进入,但这种活性在恢复期血浆中对SARS-CoV-2关注变体(VOC)的特性尚不明确。在这项研究中,我们评估了在SARS-CoV-2恢复期血浆存在下,fc介导的病毒进入(FVE)在表达fc γ riia的HEK293细胞上的作用,并将其与表达ace2的HEK293细胞中和SARS-CoV-2假病毒的作用进行了比较。在大流行早期收集了39人的血浆。我们观察到31%的血浆对感染的华盛顿SARS-CoV-2株有中和作用和FVE, 61%的血浆有中和作用,但没有FVE, 8%的血浆没有中和作用或FVE。中和效价与血浆稀释度显著相关,在血浆稀释度下观察到最大FVE,表明在中和效价减弱时,fc介导的摄取达到峰值。虽然在介导FVE的血浆和未介导FVE的血浆中,spike特异性血浆IgG水平相似,但在未介导FVE的血浆中,spike特异性血浆IgM水平明显更高。血浆对α (B.1.1.7)、β (B.1.351)、γ (P.1)和δ (B.1.617.2)挥发性有机化合物的中和效价显著低于对华盛顿菌株的中和效价,而血浆FVE对挥发性有机化合物的中和效价要么更高,要么相似。这是第一个证明恢复期血浆抗体的功能转变的报告,从中和和FVE介导早期华盛顿菌株,到仅介导FVE而不中和新出现的VOC,特别是Beta (B.1.351)和Gamma (P.1) VOC。确定这些发现在体内的相关性是很重要的。
Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants of Concern (VOC) is undefined. In this study, we evaluated Fc-mediated viral entry (FVE) on FcγRIIa-expressing HEK293 cells in the presence of SARS-CoV-2 convalescent plasma and compared it with SARS-CoV-2 pseudovirus neutralization using ACE2-expressing HEK293 cells. The plasma were collected early in the pandemic from 39 individuals. We observed both neutralization and FVE against the infecting Washington SARS-CoV-2 strain for 31% of plasmas, neutralization, but not FVE for 61% of plasmas, and no neutralization or FVE for 8% of plasmas. Neutralization titer correlated significantly with the plasma dilution at which maximum FVE was observed, indicating Fc-mediated uptake peaked as neutralization potency waned. While total Spike-specific plasma IgG levels were similar between plasma that mediated FVE and those that did not, Spike-specific plasma IgM levels were significantly higher in plasma that did not mediate FVE. Plasma neutralization titers against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC were significantly lower than titers against the Washington strain, while plasma FVE activity against the VOC was either higher or similar. This is the first report to demonstrate a functional shift in convalescent plasma antibodies from neutralizing and FVE-mediating against the earlier Washington strain, to an activity mediating only FVE and no neutralization activity against the emerging VOC, specifically the Beta (B.1.351) and Gamma (P.1) VOC. It will be important to determine the in vivo relevance of these findings.
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