Comparison of five Anti-SARS-CoV-2 antibody assays across three doses of BNT162b2 reveals insufficient standardization of SARS-CoV-2 serology.

ABSTRACT

OBJECTIVES: To investigate the comparability of WHO standard referenced commercial SARS-CoV-2 antibody tests over three doses of BNT162b2 vaccine and up to 14 months. METHODS: 114 subjects (without previous SARS-CoV-2 infection or immunosuppressive medication) vaccinated with three doses of BNT162b2 were included in this study. Antibody levels were quantified 3 weeks after the first dose, 5-6 weeks and 7 months after the second dose, and 4-5 weeks and 4 months after the third dose using the Roche Elecsys SARS-CoV-2 S, the Abbott SARS-CoV-2 IgG II Quant, the DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, the GenScript cPASS sVNT and the TECO sVNT assays. RESULTS: For each time point analyzed, systematic differences are evident between the results in BAU/mL of the three antibody binding assays. The assay ratios change in a time-dependent manner even beyond administering the third dose (Roche measuring 9 and 3 times higher than Abbott and DiaSorin, respectively). However, changes decrease in magnitude with increasing time intervals from the first dose. IgG-based assays show better agreement across them than with Roche (overall correlations Abbott x DiaSorin ρ = 0.94 vs. Abbott x Roche ρ=0.89, p < 0.0001; DiaSorin x Roche ρ = 0.87, p < 0.0001), but results are not interchangeable. The sVNTs suggest an underestimation of antibody levels by Roche and slight overestimation by both IgG assays after the first vaccine dose. CONCLUSIONS: Standardization of SARS-CoV-2 antibody binding assays still needs to be improved to allow reliable use of variable assay systems for longitudinal analyses.