Mass-Standardised Differential Antibody Binding to a Spectrum of SARS-CoV-2 Variant Spike Proteins: Wuhan, Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.4/5, BA.2.75 and BA.2.12.1 Variants-Antibody Immunity Endotypes.

A fully mass-standardised quantitative comparative analysis of the differential antibody binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan, Alpha, Beta, Gamma, Delta and the Omicron variants BA.1, BA.2.12.1, BA.2.75, BA.4 and BA.5. Evolution of immunity through five patient cohorts (n = 148 in total) was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A population of immunity endotypes has been observed and is classified against a recovery antibody threshold, with concentrations below this threshold being regarded as a 'dropout': U(+) showing protection to all variants; U(±) with single, double, triple and further dropout endotypes; and U(-) with all variant concentrations being under the threshold. The U(+) incidence rises significantly following multiple rounds of vaccination reaching an (n = 41) incidence of 54% (95% CI 39%-68%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection. The U(+) epitopes are targeted preferentially to the S1 region. U(±), with at least one dropout, has an incidence of 42% (95% CI 28%-57%), an immunity gap. Further, a U(-) sub-cohort of the population up to 13% does not make antibodies above the threshold and may not have a sterilising serum leading to persistent virus and a risk of Long COVID.