ABSTRACT
A fully quantitative comparative analysis has been performed on the differential antibody binding to a spectrum of Spike proteins to the SARS-CoV-2 variants Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.1, BA.4, BA.5, BA.2.75 and BA.2.12.1. The immunity profile was determined for four patient cohorts: pre-pandemic, the first infection in the pandemic, Wuhan(+), and two vaccinated cohorts, the initial double-vaccination with AstraZeneca (AZ) and Pfizer and a final boosted cohort including with known vaccination but unknown mixture of natural infection. A universal protection immunity endotype, U(+), with significant antibody levels to all ten variants was observed in with a incidence of 11% (95% CI 4% - 25%) in the Wuhan(+) cohort challenging directly the one-and-done immunity claim. The U(+) incidence rises to 22% (95% CI 12% - 37%) in the double-vaccinated cohort and 54% (95% CI 39% - 68%) in the triple vaccinated cohort. The remaining patients in each cohort show a spectrum of immunity with some drop-out immunity endotypes, U({+/-}), showing poor antibody response to one or more variants. The U({+/-}) incidence in the triple vaccination cohort is 41% (95% CI 28% - 57%) suggesting patients with poor sterilising sera may not clear a SARS-CoV-2 infection leading to viral persistence and mobile microcolonies that may provide a pathophysiology for the symptoms of long Covid.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
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.