Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants.

IF 8.4 2区 医学 Q1 IMMUNOLOGY Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-01-30 DOI:10.1080/22221751.2024.2307510
Frédéric Coutant, Franck Touret, Jean-Jacques Pin, Marina Alonzo, Cécile Baronti, Sandie Munier, Mikaël Attia, Xavier de Lamballerie, Tristan Ferry, Pierre Miossec
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Abstract

Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants. B cells from 13 convalescent patients originally infected by D614G or Alpha variants were immortalized to isolate 445 naturally-produced anti-SARS-CoV-2 Abs. Monoclonal antibodies (mAbs) were tested for their abilities to impact the cytopathic effect of D614G, Delta, and Omicron (BA.1) variants. Ninety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. Thirty-eight mAbs enhanced infectivity of SARS-CoV-2. Infection with D614G/Alpha variants generated variant-specific (65 neutralizing Abs, 35 enhancing Abs) and cross-reactive (18 neutralizing Abs, 3 enhancing Abs) mAbs. Interestingly, among the neutralizing mAbs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the Delta and Omicron variants. In contrast, cross-reactive mAbs enhancing infectivity (n = 3) were found exclusively specific to Delta and Omicron variants. Notably, two mAbs that amplified in vitro the cytopathic effect of the Delta variant also exhibited neutralization against Omicron. These findings shed light on functional diversity of cross-reactive Abs generated during SARS-CoV-2 infection and illustrate how the balance between neutralizing and enhancing Abs facilitate variant emergence.

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SARS-CoV-2 康复患者体内的中和抗体和增强单克隆抗体:从早期变异感染中汲取的教训以及对塑造新变异病毒的影响。
摘要对 COVID-19 康复患者进行的血清学研究发现了多克隆系特异性抗体和交叉反应性抗体(Abs),它们对病毒变种具有不同的效应功能。迄今为止,对抗 SARS-CoV-2 抗体的个体特异性及其对其他变体感染性的影响研究甚少。在此,我们在单克隆水平上剖析了早期变种引起的中和抗体和增强抗体,以及它们如何影响新变种的感染性。我们对 13 名最初被 D614G 或 Alpha 变种感染的康复患者的 B 细胞进行了永生化处理,以分离出 445 个天然产生的抗 SARS-CoV-2 抗体。对单克隆抗体(mAbs)影响 D614G、Delta 和 Omicron(BA.1)变体细胞病理效应的能力进行了测试。98种抗体对三种变体类型中的至少一种表现出强有力的中和作用,309种抗体对感染性的影响极小或没有影响。38 种 mAbs 增强了 SARS-CoV-2 的感染性。感染 D614G/Alpha 变体产生了变体特异性(65 个中和抗体,35 个增强抗体)和交叉反应性(18 个中和抗体,3 个增强抗体)mAbs。有趣的是,在对三种变体中的两种变体具有交叉反应的中和 mAbs 中,没有一种对 Delta 和 Omicron 变体表现出特异性中和作用。相比之下,增强感染性的交叉反应 mAbs(n = 3)只对 Delta 和 Omicron 变体具有特异性。值得注意的是,有两种 mAbs 在体外放大了 Delta 变体的细胞病理效应,它们也表现出了对 Omicron 的中和作用。这些发现揭示了在 SARS-CoV-2 感染过程中产生的交叉反应抗体的功能多样性,并说明了中和抗体与增强抗体之间的平衡如何促进变异体的出现:试验注册:ClinicalTrials.gov identifier:NCT04354766.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Emerging Microbes & Infections
Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY
CiteScore
26.20
自引率
2.30%
发文量
276
审稿时长
20 weeks
期刊介绍: Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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