High Heterogeneity of Virus-Neutralizing and RBD-Binding Activities of COVID-19 Convalescent Sera

Astakhova, E. A.; Byazrova, M. G.; Yusubalieva, G M; Larichev, V F; Baklaushev, V P; Filatov, A. V.

doi:10.1134/S002689332206005X

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High Heterogeneity of Virus-Neutralizing and RBD-Binding Activities of COVID-19 Convalescent Sera

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Author(s): E. A. Astakhova ¹ ^, ² , M. G. Byazrova ¹ ^, ² ^, ³ , G. M. Yusubalieva ⁴ , V. F. Larichev ⁵ , V. P. Baklaushev ⁴ , A. V. Filatov ¹ ^, ² ^,

Publication date (Electronic): 9 December 2022

Journal: Molecular Biology

Publisher: Pleiades Publishing

Keywords: COVID-19, SARS-CoV-2, virus neutralizing antibodies, human plasma, convalescents

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Abstract

The parameters of the humoral response are an important immunological characteristic of donors who recovered from COVID-19 and vaccinated individuals. Analysis of the level of virus-binding antibodies has become widespread. The most accurate predictor of effective immune protection against symptomatic SARS-CoV-2 infection is the activity of virus-neutralizing antibodies. We determined virus-neutralizing activities in plasma samples of individuals ( n = 111) who had COVID-19 from April to September 2020. Three independent methods were used: conventional with live virus, with virus-like particles pseudotyped with spike protein, and a surrogate virus-neutralization test (cVNT, pVNT and sVNT, respectively). For comparison, the levels of IgG, IgA and IgM antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein were also evaluated. The levels of virus-binding as well as virus-neutralizing antibodies in cVNT and pVNT showed high heterogeneity. A comparison of cVNT and pVNT results showed a high correlation, sVNT results also correlated well with both cVNT and pVNT. To the greatest extent, the level of IgG antibodies correlated with the results of cVNT, pVNT and sVNT. These results can be used in the selection of plasmas that are best suited for transfusion and treatment of acute COVID-19. In addition, data on the virus-neutralizing activity of plasma are important for the selection of potential donors, for the isolation of SARS-CoV-2-specific B-lymphocytes, in order to further generate monoclonal virus-neutralizing antibodies.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

David Khoury, Deborah Cromer, Arnold Reynaldi … (2021)

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

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A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction

Chee Wah Tan, Wan Ni Chia, Xijian Qin … (2020)

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.

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Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses

Shibo Jiang, Christopher Hillyer, Lanying Du (2020)

Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs.

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Author and article information

Contributors

A. V. Filatov: avfilat@yandex.ru

Journal

Journal ID (nlm-ta): Mol Biol

Journal ID (iso-abbrev): Mol Biol

Title: Molecular Biology

Publisher: Pleiades Publishing (Moscow )

ISSN (Print): 0026-8933

ISSN (Electronic): 1608-3245

Publication date (Electronic): 9 December 2022

Publication date (Print): 2022

Volume: 56

Issue: 6

Pages: 1028-1035

Affiliations

[1 ]GRID grid.465277.5, National Research Center “Institute of Immunology”, Federal Medical-Biological Agency, ; 115522 Moscow, Russia

[2 ]GRID grid.14476.30, ISNI 0000 0001 2342 9668, Immunology Department, Biological Faculty, Moscow State University, ; 119234 Moscow, Russia

[3 ]GRID grid.77642.30, ISNI 0000 0004 0645 517X, Рeoples Friendship University of Russia (RUDN University) of Ministry of Science and Higher Education of Russia, ; 117198 Moscow, Russia

[4 ]GRID grid.465277.5, Federal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies, Federal Medical-Biological Agency, ; 115682 Moscow, Russia

[5 ]GRID grid.415738.c, ISNI 0000 0000 9216 2496, Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, ; 123098 Moscow, Russia

Article

Publisher ID: 8418

DOI: 10.1134/S002689332206005X

PMC ID: 9734827

SO-VID: 6e770535-f946-4687-b05b-2269fc770bf6

Copyright © © Pleiades Publishing, Inc. 2022, ISSN 0026-8933, Molecular Biology, 2022, Vol. 56, No. 6, pp. 1028–1035. © Pleiades Publishing, Inc., 2022.Russian Text © The Author(s), 2022, published in Molekulyarnaya Biologiya, 2022, Vol. 56, No. 6, pp. 1095–1103.

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.