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

Abstract

AbstractHumanised recombinant antibodies specific to the SARS-CoV-2 Spike protein were calibrated against the NISTmAb standard human antibody to produce a fully quantitative antibody assay. The assay allows comparative studies between patient cohorts to be performed from which common properties may be derived. Two cohorts comparing patient vaccine response to AstraZeneca ChAdOx1-S (AZ, 35 patients) and Pfizer/BioNTech BNT162b2 (Pfizer, 25 patients) shows close association of the 31st percentile of the AZ distribution (2.90 ± 1.10 mg/L) and the 7th percentile of the Pfizer distribution (1.11 ± 1.10 mg/L) corresponding to the efficacy of the vaccines at preventing infection. The AZ IgG response distribution varies from 0.6 mg/L–25.4 mg/L with an average (mode) of 3.3 ± 1.0 mg/L; the Pfizer response distribution varies from 0.6 mg/L to 33.1 mg/L with a mode of 3.7 ± 1.0 mg/L. A third patient cohort looked at the recovery of 195 SARS-CoV-2 RT-PCR-positive patient samples and 200 pre-pandemic patient samples. A fourth patient cohort reviewed the NIBSC Anti-SARS-CoV-2 Verification Panel. The diagnostic cut-off for RT-PCR-positive patient samples was 1.34 ± 1.10 mg/L and the NIBSC panel separated seropositive and seronegative samples at 1.90 ± 1.10 mg/L. The mean value of the two prevention and two recovery thresholds is 1.8 mg/L with 95% confidence limits of 0.2–3.4 mg/L. In recovery and, critically, infection prevention, an antibody concentration threshold estimate of 3.4 mg/L appears mechanistically important. An antibody immunity threshold predicting a mucosal concentration preventing SARS-CoV-2 colonisation of the nasopharyngeal cavity is discussed.