Speaking the Same Language: Use of the 1 st WHO International SARS-CoV-2 Immunoglobulin Standard to Achieve Comparability Between Commercial SARS-CoV-2 Binding Antibody Assay Readouts

Background: From national SARS-CoV-2 serosurveillance programmes to COVID-19 vaccine development, a range of SARS-CoV-2 serology assays are being used. Without standardisation of assay readouts, comparison between studies by different organisations, regions or nations is challenging and will hamper recovery from the effects of the pandemic. Towards the goal of harmonisation of serology assay readouts, in 2021, WHO commissioned the HARMONY study to calibrate some of the most widely used commercial SARS-CoV-2 spike protein binding antibody assays relative to the first WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (NIBSC code: 20/136).Methods: Diagnostic test manufacturers participating in the HARMONY study were provided with three standard preparations: the 1st IS, the NIBSC anti-SARS-CoV-2 Antibody Diagnostic Calibrant (code 20/162) and the US SARS-CoV-2 serology standard (Frederick National Laboratory for Cancer Research). Manufacturers followed a standardised study protocol to titrate their in-house reference/calibrant (IHR) and the 3 standards, performing each experiment on 3 separate occasions. Results were submitted for centralised statistical analysis of dose-response curve data and calculation of potency estimates relative to the IS, expressed in binding antibody units (BAU) per millilitre (BAU/mL).Findings: Fourteen manufacturers took part in the study submitting results from 22 different test/target combinations. Each manufacturer’s IHR material was successfully calibrated against the 1st IS and assigned a unitage in BAU/mL relative to the IS. Quantification of IgG levels in BAU/mL for each secondary standard showed harmonisation of results for assays measuring binding to the same antigenic target [receptor binding domain (RBD), S1, or spike].Interpretation: This provides proof-of-concept that for the biologically important SARS-CoV-2 spike protein, levels of anti-RBD, S1 or spike IgG binding antibodies can successfully be compared across a range of well-validated commercial assays with different designs and formats through prior calibration and reporting in standardised units.Funding Information: This study was conducted through the WHO Solidarity II programme on SARS-CoV-2 seroepidemiology funded by the Swiss Agency for Development and Cooperation.Declaration of Interests: All authors declare no competing interests.