Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes

A fully mass-standardised quantitative comparative analysis of the differential 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. U(+) showing protection to all variants; single, double, triple, and further 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 = 41) there is a U(+) incidence of 54% (95% CI 39% - 68%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection; and U({+/-})) with at least one dropout has an incidence of 42% (95% CI 28% - 57%). Extending the cohort incidence to the population, up to 68% 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: up to 13% may not have a sterilising serum leading persistent virus and a risk of long covid.