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

Area of Science:

• Virology
• Immunology
• Assay Development

Background:

• SARS-CoV-2 evolution complicates neutralizing antibody testing.
• Wildtype-based assays are insufficient for predicting Omicron variant neutralization.

Purpose of the Study:

• Develop and validate an omicron-specific flow cytometry-based neutralizing antibody (FC-NAb) assay.
• Assess the FC-NAb assay's concordance with the gold standard PRNT assay.
• Evaluate the FC-NAb assay's ability to predict neutralization of Omicron subvariants like XBB.1.5.

Main Methods:

• Developed a novel omicron-specific flow cytometry-based neutralizing antibody (FC-NAb) assay.
• Compared FC-NAb assay accuracy against an omicron-specific PRNT assay.
• Assessed neutralization of XBB.1.5 using a dedicated assay.

Main Results:

• The omicron FC-NAb assay showed excellent concordance with the omicron PRNT assay (AUC=0.97, sensitivity=94%, specificity=100%).
• A strong linear relationship was observed between the omicron FC-NAb assay and XBB.1.5 neutralization (r=0.83).
• The FC-NAb assay demonstrated strong predictive performance for XBB.1.5 neutralizing activity (AUC=0.96).

Conclusions:

• The developed omicron FC-NAb assay is a reliable predictor of neutralizing activity against SARS-CoV-2 Omicron subvariants, including XBB.1.5.
• This assay provides a valuable tool for assessing immune status despite ongoing viral evolution.