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

TL;DR

A new test for omicron-specific antibodies accurately predicts neutralizing activity against the XBB 1.5 variant of SARS-CoV-2.

Contribution

A flow cytometry-based assay for omicron-specific neutralizing antibodies that predicts activity against newer subvariants like XBB 1.5.

Findings

The omicron FC-NAb test showed strong agreement with the omicron PRNT assay (AUC = 0.97).

The test strongly predicted XBB 1.5 neutralizing activity (AUC = 0.96, r = 0.83).

High sensitivity and specificity were observed for both omicron and XBB 1.5 predictions.

Abstract

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.

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.

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%).

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.

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