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早期使用康复期血浆治疗新冠病毒病对严重急性呼吸综合征冠状病毒2抗体反应的影响。

The effect of early COVID-19 treatment with convalescent plasma on antibody responses to SARS-CoV-2.

作者信息

Chan Andy Kwan Pui, Suwanmanee San, Casadevall Arturo, Shoham Shmuel, Bloch Evan M, Gebo Kelly A, Tobian Aaron A R, Pekosz Andrew, Klein Sabra L, Sullivan David, Griffin Diane E

机构信息

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

出版信息

Microbiol Spectr. 2025 Jul;13(7):e0300624. doi: 10.1128/spectrum.03006-24. Epub 2025 Jun 9.


DOI:10.1128/spectrum.03006-24
PMID:40488473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12211001/
Abstract

At the COVID-19 pandemic onset, convalescent plasma, collected from patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, emerged as a potential treatment option, but the effect on the patient immune response was unclear. To determine treatment effect on the infection antibody response, plasma samples were collected through 90 days from 104 SARS-CoV-2-infected participants after receiving CCP or control plasma, as part of a multicenter, double-blind, randomized, controlled early treatment trial. Enzyme immunoassay (EIA) was used to quantify binding IgG, IgA, and IgM to nucleocapsid (N) protein and IgG to the USA-WA1/2020 spike (S) protein. Avidity assessed antibody maturation. CCP transfusion boosted post-transfusion plasma levels of N-specific IgG, but not IgA or IgM and had a lesser effect on S-specific IgG. Over the first 2 weeks, both trial arm groups generated IgM, IgA, and IgG to N and IgG to S with comparable levels at 14-90 days after transfusion. Levels of IgM and IgA subsequently declined, while IgG was maintained through day 90 for both interventions. Avidity of N-specific IgG increased steadily over the 3-month follow-up in both groups, but S-specific IgG avidity improved only for those in the CCP group. Improved antibody titer correlated with improved avidity over time in both groups. Antibody levels and avidity between early ves late transfusion from symptom onset by trial arm intervention were also similar. In summary, CCP administration had no negative effects on the humoral response to SARS-CoV-2 infection and was associated with qualitatively improved antibodies with higher avidity.IMPORTANCEMonoclonal antibody infusion prevented COVID-19 hospitalizations. However, the massive monoclonal antibody dose, near 7% of total circulating antibodies, has been shown to decrease patient generation of SARS-CoV-2 specific IgM and lower responses to vaccination, possibly by decreasing generation of high avidity neutralization epitopes near the monoclonal binding epitope. We characterized diverse antibody population quality and quantity among intervention groups in the polyclonal COVID-19 convalescent plasma (CCP) randomized control trial, effective in reducing hospitalizations by more than 50% in all participants and 80% in those receiving transfusions with symptom onset before 5 days. Importantly, we observed a greater anti-nucleocapsid compared to anti-Spike antibody level immediately after transfusion. CCP compared to controls did not alter IgG, IgA, or IgM to nucleocapsid or IgG-spike. CCP was associated with greater IgG-nucleocapsid and, to a lesser extent, IgG-spike avidity maturation over follow-up compared to control. CCP transfusions lacked negative effects on antibody levels and avidity.

摘要

在新冠疫情爆发之初,从严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染康复患者体内采集的恢复期血浆成为一种潜在的治疗选择,但对患者免疫反应的影响尚不清楚。为了确定治疗对感染抗体反应的效果,作为一项多中心、双盲、随机、对照早期治疗试验的一部分,在104名感染SARS-CoV-2的参与者接受新冠恢复期血浆(CCP)或对照血浆后,在90天内收集血浆样本。采用酶免疫测定(EIA)法对与核衣壳(N)蛋白结合的IgG、IgA和IgM以及与USA-WA1/2020刺突(S)蛋白结合的IgG进行定量。亲和力评估抗体成熟度。输注CCP可提高输血后血浆中N特异性IgG水平,但对IgA或IgM无影响,对S特异性IgG的影响较小。在最初的2周内,两个试验组均产生了针对N的IgM、IgA和IgG以及针对S的IgG,输血后14 - 90天水平相当。随后,IgM和IgA水平下降,而两种干预措施的IgG水平在第90天仍保持稳定。在3个月的随访中,两组N特异性IgG的亲和力均稳步增加,但只有CCP组的S特异性IgG亲和力有所改善。随着时间的推移,两组抗体滴度的提高与亲和力的改善相关。按试验组干预措施,症状出现后早期和晚期输血之间的抗体水平和亲和力也相似。总之,输注CCP对SARS-CoV-2感染的体液反应没有负面影响,且与亲和力更高、质量得到定性改善的抗体有关。

重要性 单克隆抗体输注可预防新冠住院。然而,大量的单克隆抗体剂量(接近循环抗体总量的7%)已被证明会减少患者产生的SARS-CoV-2特异性IgM,并降低对疫苗接种的反应,可能是通过减少单克隆结合表位附近高亲和力中和表位的产生。我们在多克隆新冠恢复期血浆(CCP)随机对照试验中对各干预组中不同抗体群体的质量和数量进行了表征,该试验在所有参与者中有效降低住院率超过50%,在症状出现前5天接受输血的参与者中降低80%。重要的是,我们观察到输血后立即出现的抗核衣壳抗体水平高于抗刺突抗体水平。与对照组相比,CCP对核衣壳或IgG - 刺突的IgG、IgA或IgM没有改变。与对照组相比,在随访期间,CCP与更高的IgG - 核衣壳以及在较小程度上更高的IgG - 刺突亲和力成熟相关。输注CCP对抗体水平和亲和力没有负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/159238f3bddd/spectrum.03006-24.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/057b373a1a20/spectrum.03006-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/7596347ea4bd/spectrum.03006-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/9af9750ba258/spectrum.03006-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/e77986930ce6/spectrum.03006-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/690034df9c90/spectrum.03006-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/159238f3bddd/spectrum.03006-24.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/057b373a1a20/spectrum.03006-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/7596347ea4bd/spectrum.03006-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/9af9750ba258/spectrum.03006-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/e77986930ce6/spectrum.03006-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/690034df9c90/spectrum.03006-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e4/12211001/159238f3bddd/spectrum.03006-24.f006.jpg

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本文引用的文献

[1]
SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback.

J Infect Dis. 2024-11-15

[2]
COVID-19 drug discovery and treatment options.

Nat Rev Microbiol. 2024-7

[3]
Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

JCI Insight. 2024-3-14

[4]
Antibody-Mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans.

J Infect Dis. 2024-2-14

[5]
COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response.

JCI Insight. 2023-4-24

[6]
Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

Clin Infect Dis. 2023-6-16

[7]
Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

Ann Intern Med. 2022-9

[8]
The anti-SARS-CoV-2 monoclonal antibody bamlanivimab minimally affects the endogenous immune response to COVID-19 vaccination.

Sci Transl Med. 2022-7-27

[9]
Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

N Engl J Med. 2022-5-5

[10]
Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response.

Clin Immunol. 2022-3

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