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SARS-CoV-2 感染的纵向系统和黏膜免疫应答。

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

机构信息

Division of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Dartmouth College, Hanover, New Hampshire, USA.

出版信息

J Infect Dis. 2022 Sep 28;226(7):1204-1214. doi: 10.1093/infdis/jiac065.

DOI:10.1093/infdis/jiac065
PMID:35188974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8903457/
Abstract

BACKGROUND

A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

METHODS

Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays.

RESULTS

Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman ρ = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (ρ = 0.52), disease severity (ρ = 0.59), and age (ρ = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ = 0.42) and IgA (ρ = 0.63).

CONCLUSIONS

Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission.

摘要

背景

本纵向研究旨在确定严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染后系统和黏膜抗体应答的广度、动力学和相关性。

方法

26 名未经疫苗接种的新冠肺炎确诊患者在 6 个月的时间里接受了 3 次血液、鼻腔分泌物和粪便采集。对照组来自 16 名未经疫苗接种的未感染者。分别通过假病毒检测和多重珠粒阵列评估 SARS-CoV-2 中和抗体和结合抗体应答。

结果

26 名感染者的血清和呼吸道样本中分别有 96%(25/26)和 54%(14/26)检测到针对 SARS-CoV-2 的中和抗体应答。在血清和呼吸道鼻腔分泌物中均检测到针对 SARS-CoV-2 刺突蛋白及其 S1、S2 和受体结合(RBD)结构域的强结合抗体应答,但在粪便样本中未检测到。血清中和与血清中 RBD 特异性 IgG、IgM 和 IgA 呈正相关(Spearman ρ=0.74、0.66 和 0.57),与呼吸道分泌物中的 RBD 特异性 IgG 呈正相关(ρ=0.52),与疾病严重程度呈正相关(ρ=0.59),与年龄呈正相关(ρ=0.40)。呼吸道黏膜中和与 RBD 特异性 IgM(ρ=0.42)和 IgA(ρ=0.63)呈正相关。

结论

SARS-CoV-2 感染后可产生持续的抗体应答。值得注意的是,在全身和呼吸道部位可独立诱导 IgM 和 IgA 结合抗体和中和抗体应答。这些观察结果对当前的疫苗策略以及对 SARS-CoV-2 再感染和传播的理解具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/765d642b871c/jiac065_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/021753b577a4/jiac065_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/ec04a502784d/jiac065_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/75a05f5ce7bb/jiac065_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/12091f3884fa/jiac065_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/765d642b871c/jiac065_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/021753b577a4/jiac065_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/ec04a502784d/jiac065_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/75a05f5ce7bb/jiac065_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/12091f3884fa/jiac065_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/9518838/765d642b871c/jiac065_fig5.jpg

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