Antibody Affinity Maturation to SARS-CoV-2 Omicron Variants in a Teachers Cohort

Abstract

AbstractIn summer of 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.