ABSTRACT
In July 2022, a cohort of 28 staff members were recruited from a UK primary school setting. The prevalent variants at the time were Omicron BA.1.159, BA.4/5 and BA.2: 61% of the cohort reported a lateral flow confirmed positive test for SARS-CoV-2 infection in late 2021 or 2022. A fully quantitative antibody screen for concentration and affinity was performed for spike protein variants Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.2.75, BA.2.12.1, BA.4 and BA.5 and a pH dependent affinity was derived from disruption of the epitope-paratope complex at pH 3.2. The cohort showed a Universal positive immunity endotype, U(+), incidence of 78% (95% CI 60% - 88%) with good antibody concentrations to all ten variants; the incidence drops to 25% (95% CI 13% - 43%) when the affinity spectrum is measured. The antibody affinity profiles for each Omicron variant were all significantly better than Alpha, Beta, Gamma and Delta reflecting exposure to the antigens; we surmise either from the booster vaccines or continual contact with the virus, presenting in the school children either asymptomatically or symptomatically. Significant antibody affinity maturation was seen to the spike protein in all prevalent variants of SARS-CoV-2. Antibody concentrations were waning compared to the post-booster vaccine response. Using our hypothesised 3.4 mg/L nasal mucosal protection threshold, we postulate 46% of the cohort required boosting within 60 days and 66% within 120 days. We propose a smart boosting programme around the constant-exposure teacher cohort and parents of children could reduce community transmission.
Subject(s)
COVID-19ABSTRACT
A fully quantitative comparative analysis of the differential binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan (ancestral strain), Alpha, Beta, Gamma, Delta and Omicron BA.1. Evolution of immunity through five patient cohorts was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A series of immunity endotypes has been observed: U(+) showing protection to all variants; single, double, triple, quadruple and quintuple dropout endotypes U({+/-}); some with no variant protection other than Wuhan vaccine spike U(-); and some unclassified, U([~]). These endotypes may be imprinted. In the triple-vaccinated cohort (n = 54) there is a U(+) incidence of 65% (95% CI 51% - 76%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection; U(-) 6% (95% CI 2% - 15%) of the population have no variant antibody protection provided by the vaccine; and U({+/-})) with at least one dropout has a incidence of 20% (95% CI 12% - 33%). Extending the cohort incidence to the population, up to 76% of the population may have an imprinted immunity endotype to an epitope that is effective against all variants; critical for both protection and binding to the ACE2 receptor: a universal immunity endotype. However, up to 33% of the population may have an immunity endotype that will never produce an effective antibody response to SARS-CoV-2 unless the immunity imprint is broken. FundingExeter University Alumni, Attomarker Ltd funded PhD studentship at the University of Exeter and Attomarker Ltd funding directly.
ABSTRACT
Humanised 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.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
The SARS-CoV-2 Omicron variant (BA.1) has 25 unique mutations to the Spike glycoprotein, suggesting the efficacy of current vaccines against the new variant may be seriously degraded. A fully quantitative antibody binding study was performed for Spike Omicron (SO) and original Spike (S) proteins simultaneously on three cohorts of patients: convalescent following RT-PCR-confirmed infection in early 2020, double-vaccinated at [≥]2 weeks, and vaccine boosters. The average (mode) of the booster cohort response distributions were 15.1 mg/L and 13.4 mg/L for S and SO, respectively, compared with the significantly lower double-vaccinated average, S=2.4 mg/L, SO=2.0 mg/L, and natural infections average S=2.0 mg/L, SO = 1.8 mg/L. A preliminary epitope degradation screen was performed for a panel of antibodies raised to the S1 and S2 regions of the original S protein. The panel showed significant degradation to antibody epitopes in the S1 region. Differential antibody binding of the vaccine response to S and SO suggests vaccine efficacy may be reduced by up to 50% against the Omicron variant.