Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Neutralizing antibodies are crucial for COVID-19 protection.
• Previous vaccine trials used binding antibody thresholds as surrogates for neutralization.
• The predictive value of these thresholds against SARS-CoV-2 variants of concern (VOCs) and its dependence on immune history remain unclear.

Purpose of the Study:

• To determine if binding antibody thresholds can predict sufficient neutralizing capacity against VOCs.
• To assess the impact of vaccine or infection history on this predictive relationship.
• To establish a reliable antibody threshold for predicting protection against current SARS-CoV-2 strains.

Main Methods:

• Analysis of individuals with SARS-CoV-2 infection, vaccination, or hybrid immunity.
• Correlation of receptor binding domain (RBD) IgG levels with neutralizing antibody titers (NT50) against wild-type (WT) and VOCs.
• Validation of a proposed RBD IgG threshold (456 BAU/mL) against WT NT50 ≥ 1000 IU across different immune histories.

Main Results:

• An RBD IgG level of 456 BAU/mL accurately predicts a WT NT50 of 1000 IU (80% accuracy) in unvaccinated convalescent individuals.
• This threshold maintains accuracy in predicting loss of protective immunity against VOCs in vaccinated cohorts.
• It accurately predicts NT50 < 100 IU against the Beta variant in 2-dose vaccine recipients (80% accuracy) and against BA.5 in hybrid immunity recipients (87% accuracy).

Conclusions:

• A specific RBD IgG threshold (456 BAU/mL) can serve as a reliable surrogate marker for predicting neutralizing antibody levels against SARS-CoV-2 VOCs.
• This threshold is effective across diverse immune histories, including vaccination and hybrid immunity.
• The findings provide a discrete, clinically applicable threshold for assessing protective immunity in future studies and potentially in public health strategies.