Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity

Abstract

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen–antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6–8 months regardless of the subsequent change in the antibody levels.

High Concentration of Anti-SARS-CoV-2 Antibodies 2 Years after COVID-19 Vaccination Stems Not Only from Boosters but Also from Widespread, Often Unrecognized, Contact with the Virus

“…Staerke et al showed that this was true for the Delta variant of SARS-CoV-2, but the risk of breakthrough infection with Omicron was not related to anti-S IgG concentrations [49]. Although some efforts have been put towards establishing an antibody protective titer [51,[54][55][56], neither a universal cut-off for protection nor a definition of a "high" antibody concentration have been proposed yet. Dimeglio et al reported that anti-S-RBD antibody concentrations of 1700 BAU/mL and above provided full protection in subjects followed-up for a median of 275 days (ca.…”

Serologic evidence for early SARS-CoV-2 circulation in Lima, Peru, 2020

“…Additionally, these samples showed a statistically higher mean S-based avidity of 126.4% and lower NCP-based avidity of 11.0% compared to samples from April 2020 onward (S t-test=2.4, p=0.01; NCP t-test=-2.9, p=0.007; Figure 1E and 1F). High avidity to the S protein is reached 1-2 months after SARS-CoV-2 infection and is maintained for approximately 6-8 months (8,9). High S-based avidity would thus suggest very early SARS-CoV-2 infection in patients sampled during January 2020, contrasting with calculated SARS-CoV-2 phylogenetic introduction estimates and the first SARS-CoV-2 molecular detections in Latin America dating from February 2020 onwards (10).…”