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COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants

Daniel Junker1, Alex Dulovic1, Matthias Becker1

  • 1NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770, Reutlingen, Germany.

Scientific Reports
|May 3, 2022
PubMed

Insights

A new assay measures neutralizing antibodies against SARS-CoV-2 variants. This method shows reduced antibody binding to variants like Beta and Gamma, correlating with IgG levels and disease severity.

Area of Science:

  • Immunology
  • Virology
  • Biotechnology

Background:

  • Neutralizing antibodies (Nabs) targeting the SARS-CoV-2 receptor binding domain (RBD) are crucial for immune protection against COVID-19.
  • The emergence of SARS-CoV-2 variants of concern (VOCs) poses challenges to vaccine efficacy due to altered ACE2 receptor binding and reduced neutralization.
  • Assessing immune responses against diverse variants is vital for understanding protection longevity and informing public health strategies.

Purpose of the Study:

  • To develop and validate a scalable multiplex assay for measuring ACE2-RBD binding inhibition against SARS-CoV-2 variants.
  • To evaluate the impact of key mutations on antibody binding across different SARS-CoV-2 variants.
  • To correlate ACE2 binding inhibition with patient factors such as IgG levels and disease severity.

Main Methods:

  • Development of a bead-based multiplex ACE2-RBD inhibition assay (RBDCoV-ACE2) to simultaneously analyze binding to multiple RBD variants.
  • Validation of the assay against classical virus neutralization tests and a commercial assay.
  • Analysis of 266 serum samples from 168 COVID-19 patients with varying disease severity.

Main Results:

  • The RBDCoV-ACE2 assay demonstrated high scalability and efficiency compared to traditional methods.
  • ACE2 binding inhibition was significantly reduced for ten out of eleven SARS-CoV-2 variants tested, particularly those with the E484K mutation (e.g., Beta, Gamma).
  • ACE2 binding inhibition showed a positive correlation with IgG levels and disease severity up to WHO grade 7.

Conclusions:

  • The developed multiplex assay is a valuable tool for assessing neutralizing antibody responses against SARS-CoV-2 variants.
  • Immune responses exhibit reduced efficacy against variants carrying specific mutations, highlighting the need for variant-specific immune monitoring.
  • Antibody binding inhibition is a potential correlate of protection that varies individually and with disease severity.

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