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A Rapid, Multiplex Dual Reporter IgG and IgM SARS-CoV-2 Neutralization Assay for a Multiplexed Bead-Based Flow Analysis System
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Antibody Levels From High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike Immunoglobulin G and
Marni B Jacobs1, Alex E Clark2, Nicole H Goldhaber3
1Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, USA.
The Journal of Infectious Diseases
|December 16, 2024
Summary
Variant-specific SARS-CoV-2 antibody levels, measured by high-throughput assays, correlate with protection from infection. These methods, using dried blood spots, can help time COVID-19 booster shots.
Area of Science:
- Immunology
- Infectious Diseases
- Public Health
Background:
- Antibody levels are proposed as a correlate of protection against SARS-CoV-2 infection.
- Large-scale prospective studies on scalable antibody measures predicting real-world infection risk are limited.
Purpose of the Study:
- To assess if high-throughput, variant-specific SARS-CoV-2 anti-spike IgG and ACE2 neutralization assays correlate with cell-based neutralization measurements.
- To determine if these assays can serve as correlates of protection against SARS-CoV-2 infection.
Main Methods:
- A large institutional cohort study (N=2513) was conducted from January 2022 to March 2023.
- Dried blood spot (DBS) samples were used for high-throughput anti-spike IgG and ACE2 inhibition assays.
- Serum samples (n=105) were compared with cell-based SARS-CoV-2 neutralization assays.
Main Results:
- High correlation was observed between serum and DBS sampling, and between cell-based and high-throughput assays for anti-spike IgG and ACE2 neutralization, varying by variant.
- DBS-based IgG and ACE2 inhibition levels were inversely correlated with infection risk, with higher sensitivity for ACE2 inhibition and variant-matched measures.
- Antibody levels decreased over time, with more durable responses seen after infection compared to vaccination.
Conclusions:
- Variant-specific SARS-CoV-2 antibody levels are a potential correlate of protection, informing vaccination strategies and infection risk assessment.
- High-throughput assays using DBS samples may aid in determining optimal timing for COVID-19 booster vaccinations at population and individual levels.

