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J Med Virol . Estimating SARS-CoV-2 Omicron XBB.1.5 Spike-Directed Functional Antibody Levels From an Anti-Receptor Binding Domain Wuhan-Hu-1-Based

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Jan;97(1):e70130.
doi: 10.1002/jmv.70130. Estimating SARS-CoV-2 Omicron XBB.1.5 Spike-Directed Functional Antibody Levels From an Anti-Receptor Binding Domain Wuhan-Hu-1-Based Commercial Immunoassay Results

Ángela Sánchez-Simarro[SUP] 1 [/SUP], Enric Cuevas-Ferrando[SUP] 1 [/SUP], Daniel Fernández-Soto[SUP] 2 [/SUP], Brayan Grau[SUP] 3 [/SUP], Eliseo Albert[SUP] 1 [/SUP], Estela Giménez[SUP] 1 4 [/SUP], Ana Isabel Avilés-Alía[SUP] 3 [/SUP], Luciana Rusu[SUP] 3 [/SUP], Ron Geller[SUP] 3 [/SUP], Hugh T Reyburn[SUP] 2 [/SUP], David Navarro[SUP] 1 4 5 [/SUP]



Affiliations
Abstract

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 (R[SUP]2[/SUP] = 0.72), though models for Omicron XBB.1.5 were less robust. Anti-RBD antibody concentrations of 4.73 and 5.02 log[SUB]10[/SUB] 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 log[SUB]10[/SUB] and 4.54 log[SUB]10[/SUB] 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 log[SUB]10[/SUB] 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.

Keywords: NK cells; Omicron XBB.1.5; Random Forest modeling; Roche Elecsys® anti‐SARS‐CoV‐2 S assay; SARS‐CoV‐2; anti‐RBD total antibodies; neutralizing antibodies.

 
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