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Updated: Jun 17, 2026
Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of
Maggie Li1, Evan J Beck2, Oliver Laeyendecker2
1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Abstract:
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.
Insights
High-titer COVID-19 convalescent plasma (CCP) effectively neutralizes SARS-CoV-2 variants like Delta and Omicron. This offers a promising therapeutic option when monoclonal antibodies are limited or ineffective.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenge existing monoclonal antibody therapies.
- COVID-19 convalescent plasma (CCP) is authorized for outpatient use in immunosuppressed individuals.
- CCP's polyclonal antibody nature presents variability in neutralization capacity against evolving viral strains.
Purpose of the Study:
- To evaluate the neutralization efficacy of CCP against SARS-CoV-2 variants.
- To correlate CCP antibody levels with neutralization potency against specific variants.
- To assess the effectiveness of CCP in the context of limited therapeutic options.
Main Methods:
- Analysis of 108 pre-variant SARS-CoV-2 CCP units and 20 post-variant/post-vaccination units.
- Testing neutralization of vaccine-related isolate (WA-1), Delta (δ), and Omicron (ο) SARS-CoV-2 strains.
- Correlation of neutralization activity with Euroimmun S1 immunoglobulin G antibody levels.
Main Results:
- A 2- to 4-fold decrease in neutralization against Delta and a 20- to 40-fold decrease against Omicron compared to the WA-1 strain.
- High-titer CCP, including top 10% of pre-variant units and all post-variant/post-vaccination units, effectively neutralized all tested variants.
- A hyperimmunoglobulin preparation also demonstrated broad neutralization capacity.
Conclusions:
- High-titer CCP retains significant neutralizing activity against SARS-CoV-2 variants, including Delta and Omicron.
- CCP can be an effective therapeutic strategy against SARS-CoV-2 variants, even without prior donor exposure to those specific variants.
- The findings support the continued investigation and use of high-titer CCP as a viable treatment for COVID-19.
