Mass-Standardised Antibody Affinity Maturation to the Spike Protein of SARS-CoV-2 Omicron Variants in a Constant-Exposure Cohort: forgiving Original Antigenic Sin

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Abstract
Prevalence of SARS-CoV-2 amongst school children in the omicron wave was high leading to a constant exposure of teachers to the virus. A cohort of staff members ( n = 28) was recruited from a UK primary school setting. The prevalent variants at the time were Omicron BA.1, 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 mass-standardised quantitative antibody spectrum was measured for both antibody concentration and a new measure of antibody quality; the proportion of antibodies still bound to the epitope at pH 3.2 compared with pH 7.4. The antibody spectrum was measured or IgG to the spike protein for variants Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.2.75, BA.2.12.1, BA.4 and BA.5. The new antibody quality measure shows a mean of 49% with (IQR 32% – 68%). The cohort showed a Universal positive immunity endotype, U(+), of antibodies binding to the spike protein across the variant spectrum with an 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.

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