Fully Quantitative Measurements of the Antibody Levels for SARS-CoV-2 Infections and Vaccinations calibrated against the NISTmAb Standard IgG Antibody

A quantitative biophotonic assay for IgG antibodies for the SARS-CoV-2 spike protein has been standardised against the NISTmAb antibody. Serum from patients recovering from infection, a sterilising serum, and post-vaccination, are used to profile anti-spike protein IgG responses. The vaccine response distributions were used to quantify live-challenge protective thresholds: the 31st percentile of the AstraZeneca ChAdOx1-S (AZ, n =35 patients) distribution (2.90 {+/-} 1.10 mg/L) and the 7th percentile of the Pfizer/BioNTech BNT162b2 (Pfizer, n =25 patients) distribution (1.11 {+/-} 1.10 mg/L). The recovery serum antibody response was characterised in 195 SARS-CoV-2 RT-PCR-positive patient and compared with 200 pre-pandemic patient samples. The diagnostic cut-off for RT-PCR-positive recovering patient samples was 1.34 {+/-} 1.10 mg/L. The Anti-SARS-CoV-2 NISBC Verification Panel showed a separation of seropositive and seronegative samples at 1.90 {+/-} 1.10 mg/L. The mean mass-standardised value of the two prevention and two recovery thresholds is 1.8 mg/L (95% CI 0.2-3.4) mg/L: moving beyond correlates of protection and clearance, to mechanism. FundingThe work was funded by donations to Prof Shaws research group from the Exeter University Alumni during the pandemic, by Attomarker Ltd that funded PhD studentship for Philip James-Pemberton at the University of Exeter and Attomarker Ltd directly. Declaration of InterestProf Shaw is the Founder, CEO and Director of Attomarker Ltd, a spin-out company from his research group. Related Publications in the SeriesPaper 1 - This Paper - Mass-Standardised Quantitative Measurements of the Antibody Levels for SARS-CoV-2 beyond Correlates of Protection and Clearance Paper 2 - Mass-Standardised Differential Antibody Binding to a Spectrum of SARS- CoV-2 Variant Spike Proteins: Wuhan, Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.4/5, BA.2.75 and BA.2.12.1 variants - Antibody Immunity Endotypes Paper 3 -Mass-Standardised Antibody Affinity Maturation to the Spike Protein of SARS-CoV-2 Omicron Variants in a Constant-Exposure Cohort: Forgiving Original Antigenic Sin Paper 4 - Diagnostic Classification for Long Covid Patients identifying Persistent Virus and Hyperimmune Pathophysiologies leading to a Test-and-Treat Protocol