Estimating SARS-CoV-2 Omicron XBB.1.5 Spike-Directed Functional Antibody Levels From an Anti-Receptor Binding Domain...

We investigated whether antibody concentrations measured in plasma using the Roche Elecsys® Anti-SARS-CoV-2 S assay (targeting the receptor binding domain, RBD) could estimate levels of Wuhan-Hu-1 and Omicron XBB.1.5 spike-directed antibodies with neutralizing ability (NtAb) or those mediating NK-cell activity. We analyzed 135 plasma samples from 39 vaccinated elderly nursing home residents. A strong correlation was found for NtAb against both Wuhan-Hu-1 (Rho = 0.73, p < 0.001) and Omicron XBB.1.5 (sub)variants (Rho = 0.73, p < 0.001). Moderate positive correlations were observed for NK-cell activity, based on lysosome-associated membrane protein 1 (LAMP1)-producing NK cells stimulated with Wuhan-Hu-1 (Rho = 0.43, p < 0.001) and Omicron XBB.1.5 spike proteins (Rho = 0.50, p < 0.001). Similarly, interferon-gamma (IFN-γ)-producing NK-cell frequencies showed moderate correlations (Wuhan-Hu-1: Rho = 0.43, p < 0.001; Omicron XBB.1.5: Rho = 0.50, p < 0.001). Random Forest models accurately predicted NtAb levels against Wuhan-Hu-1 (R² = 0.72), though models for Omicron XBB.1.5 were less robust. Anti-RBD antibody concentrations of 4.73 and 5.02 log₁₀ BAU/mL predicted high NtAb levels for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. Antibody thresholds for predicting functional NK cell-mediated responses were 4.73 log₁₀ and 4.54 log₁₀ BAU/mL for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. For LAMP1-producing NK cells, the thresholds were 4.94 and 4.75 log₁₀ BAU/mL for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. In summary, total anti-RBD antibody levels measured by the Roche assay may allow inference of NtAb levels and, to a lesser extent, Fc-mediated NK-cell responses against Omicron XBB.1.5.