Anti-RBD immunoglobulin levels and their predictive value for SARS-CoV-2 neutralization

Throughout the SARS-CoV-2 pandemic, neutralizing antibody levels have been central to predict a protective immune response. Anti-receptor-binding domain (RBD) enzyme-linked immunosorbent assays (ELISAs) correlate with neutralization assays and are due to the integration of simple performance with timely results used as surrogate assays. However, previous studies determining correlation used homogeneous cohorts. We reevaluated the correlation of a frequently used anti-RBD ELISA and a live virus neutralization assay using a heterogeneous cohort consisting of a vaccinated group without prior SARS-CoV-2 infection and a vaccinated convalescent group. The neutralizing capacity of sera with matched anti-RBD units significantly differed between groups, decreasing the correlation of the assays. Our findings highlight the necessity of considering the immunization context when interpreting serological tests and suggest that different immunization groups may require distinct protective thresholds. Considering the immunization history, we can develop more accurate predictions of immunity not only for SARS-CoV-2 but also for future challenges.