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

Abstract

AbstractA 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.