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Published on: June 5, 2021
Anti-RBD immunoglobulin levels and their predictive value for SARS-CoV-2 neutralization.
Sabine Lichtenegger1, Sissy Therese Sonnleitner1, Sabine Saiger1
1Diagnostic & Research Institute of Hygiene, Microbiology and Environmental Medicine, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.
Antibody-binding assays for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) are useful but can be misleading. Sera with similar anti-receptor-binding domain (RBD) levels show varied neutralization potency, especially between vaccinated and hybrid immunity groups.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Anti-receptor-binding domain (RBD) antibody titers correlate with SARS-CoV-2 neutralization and protection.
- Antibody-binding assays (e.g., ELISA) are widely used surrogates for live virus neutralization assays due to ease of performance and lower biosafety requirements.
- Previous correlation studies often used homogeneous cohorts, potentially overlooking variations in neutralizing capacity across different immunization histories.
Purpose of the Study:
- To investigate if sera with matched anti-RBD immunoglobulin levels exhibit different neutralizing potencies based on diverse immunization and infection histories.
- To reevaluate the correlation between a widely used anti-RBD ELISA and a live virus neutralization assay using a heterogeneous cohort.
- To determine if immunization context influences the interpretation of serological tests for predicting protective immunity against SARS-CoV-2.
Main Methods:
- Sera from 27 vaccinated-only individuals and 27 SARS-CoV-2 convalescent vaccinated individuals were analyzed.
- Antibody-binding capacity was measured using the Elecsys anti-SARS-CoV-2 S enzyme-linked immunosorbent assay (ELISA).
- Neutralizing potency was assessed using a live SARS-CoV-2 virus neutralization assay.
Main Results:
- Within the vaccine and hybrid-immunized groups, anti-RBD immunoglobulin units generally correlated with virus neutralization capacity.
- Sera with matched anti-RBD units demonstrated significantly different neutralization potentials between the vaccinated-only and hybrid immunity groups.
- Hybrid immunity exhibited significantly higher neutralization potency compared to vaccinated-only sera with similar anti-RBD immunoglobulin levels.
Conclusions:
- Quantitative data from anti-RBD ELISAs require cautious interpretation, particularly when comparing individuals with different immunization histories.
- Similar anti-RBD antibody levels can correspond to markedly different functional neutralizing activity.
- These findings have implications for establishing future correlates of protection and may necessitate distinct protective thresholds for different immunization groups.
