使用标准化、定量中和测定法对关注的 SARS-CoV-2 变异株进行中和效价分析,揭示了与疾病严重程度的相关性;旨在解析保护性抗体阈值。

Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds.

机构信息

Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent & Greenwich, Chatham, United Kingdom.

Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.

出版信息

Front Immunol. 2022 Mar 7;13:773982. doi: 10.3389/fimmu.2022.773982. eCollection 2022.

Abstract

The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we examine the capacity of convalescent sera, from a well-defined cohort of healthcare workers (HCW) and Patients infected during the first wave from a national critical care centre in the UK to neutralise B.1.1.298, variants of interest (VOI) B.1.617.1 (Kappa), and four VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta), including the B.1.617.2 K417N, informally known as Delta Plus. We utilised the WHO International Standard for anti-SARS-CoV-2 Immunoglobulin to report neutralisation antibody levels in International Units per mL. Our data demonstrate a significant reduction in the ability of first wave convalescent sera to neutralise the VOCs. Patients and HCWs with more severe COVID-19 were found to have higher antibody titres and to neutralise the VOCs more effectively than individuals with milder symptoms. Using an estimated threshold for 50% protection, 54 IU/mL, we found most asymptomatic and mild cases did not produce titres above this threshold.

摘要

SARS-CoV-2 变种的出现使得定义保护相关性变得更加麻烦,尽管世界卫生组织(WHO)有抗 SARS-CoV-2 免疫球蛋白血清国际标准,这是一种用于将实验室发现标准化为国际单位的关键试剂。我们使用假型病毒,检查了来自英国国家重症监护中心的第一波感染的医护人员(HCW)和患者的恢复期血清中和 B.1.1.298、感兴趣的变体(VOI)B.1.617.1(Kappa)、四个 VOC 的能力,B.1.1.7(Alpha)、B.1.351(Beta)、P.1(Gamma)和 B.1.617.2(Delta),包括 B.1.617.2 K417N,俗称 Delta Plus。我们利用抗 SARS-CoV-2 免疫球蛋白的世界卫生组织国际标准,以国际单位/毫升报告中和抗体水平。我们的数据表明,第一波恢复期血清中和 VOC 的能力显著降低。患有更严重 COVID-19 的患者和 HCW 被发现具有更高的抗体滴度,并且能够更有效地中和 VOC。使用 50%保护的估计阈值 54 IU/mL,我们发现大多数无症状和轻症病例的滴度没有超过这个阈值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70e4/8940306/ef530deeafeb/fimmu-13-773982-g001.jpg

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