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Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Complement augments antibody neutralization of SARS-CoV-2 variants
Martin Jungbauer-Groznica1,2, Pierre Rosenbaum3, Isabelle Staropoli2
1Antiviral Activities of Antibodies Group, Institut Pasteur, Université Paris Cité, Paris, France.
The complement system significantly boosts antibody effectiveness against SARS-CoV-2 variants like JN.1. This immune cooperation enhances neutralization, particularly for variants that evade antibodies, aiding in host defense against severe COVID-19.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- The complement system is crucial for humoral immunity but its role with antibodies against SARS-CoV-2 is not fully understood.
- Understanding this interaction is key for developing effective COVID-19 therapies.
Purpose of the Study:
- To investigate how the complement system enhances antibody-mediated neutralization of SARS-CoV-2.
- To determine the impact of complement on neutralizing various SARS-CoV-2 variants, including immune-evasive ones.
Main Methods:
- Authentic virus neutralization assays.
- Antibody engineering and characterization.
- Single viral particle analysis using flow virometry.
Main Results:
- Complement increased SARS-CoV-2 neutralization titers by up to 42-fold across different immune sera and variants (D614G, BA.1, XBB.1.5, JN.1).
- Complement significantly enhanced neutralization of immune-evasive variants (XBB.1.5, JN.1), restoring neutralization in previously non-neutralizing samples.
- Enhancement involved anti-S2 antibodies and required Fc hexamerization and C1q/C3 deposition, but not C9-mediated virolysis.
Conclusions:
- Complement potentiates antibody neutralization of SARS-CoV-2, especially immune-evasive variants.
- Complement deposition on viral particles enhances neutralization without causing virolysis.
- Complement-mediated neutralization and anti-S2 antibodies correlate with improved survival in severe COVID-19.
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