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Front Immunol . An omicron-specific neutralizing antibody test predicts neutralizing activity against XBB 1.5

tetano

Editor, Senior Moderator
Front Immunol


. 2024 Jan 23:15:1334250.
doi: 10.3389/fimmu.2024.1334250. eCollection 2024. An omicron-specific neutralizing antibody test predicts neutralizing activity against XBB 1.5

Stephen Varvel[SUP] 1 [/SUP], Marzena Galdzicka[SUP] 1 [/SUP], Stephanie Nystrom[SUP] 2 [/SUP], Hong Liu[SUP] 2 [/SUP], Ge Chen[SUP] 2 [/SUP], Izabela Ragan[SUP] 3 [/SUP], Shahrokh Shabahang[SUP] 2 [/SUP]



Affiliations
Free PMC article Abstract

Introduction: Understanding the immune status of an individual using neutralizing antibody testing is complicated by the continued evolution of the SARS-CoV-2 virus. Previous work showed that assays developed against the wildtype strain of SARS-CoV-2 were insufficient predictors of neutralization of omicron variants, thus we developed an omicron-specific flow cytometry-based neutralizing antibody test and performed experiments to assess how well it compared to an omicron-specific PRNT assay (gold standard) and whether it could predict neutralizing activity to more recent omicron subvariants such as XBB.1.5.
Methods: Accuracy of a novel flow cytometry-based neutralizing antibody (FC-NAb) assay was determined by comparison with an omicron-specific PRNT assay. A series of samples were evaluated in both the omicron FC-NAb assay and a second test was designed to assess neutralization of XBB.1.5.
Results: Good concordance between the omicron FC-NAb test and the omicron PRNT was demonstrated (AUC = 0.97, p <0.001; sensitivity = 94%, specificity = 100%, PPV = 100%, and NPV = 97%). A strong linear relationship between the omicron FC-NAb and neutralization of XBB1.5 was observed (r = 0.83, p<0.001). Additionally, the omicron FC-NAb test was a very strong predictor of positive XBB1.5 NAb activity (AUC = 0.96, p<0.001; sensitivity = 94%, specificity = 90%, positive predictive value = 90%, and negative predictive values = 94%).
Discussion: Our data suggest that despite continued evolution of the SARS-CoV-2 spike protein, the omicron FC-NAb assay described here is a good predictor of XBB1.5 neutralizing activity, as evidenced by a strong correlation and good predictive performance characteristics.

Keywords: SARS-CoV-2; XBB.1.5; flow cytometry; neutralizing antibody; omicron.

 
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