Fully Quantitative Measurements of Differential Antibody Binding to a Spectrum of SARS-CoV-2 Spike Proteins: Wuhan, Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.4, BA.5, BA.2.75 and BA.2.12.1

Abstract A fully quantitative comparative analysis has been performed on the differential antibody binding to a spectrum of Spike proteins to the SARS-CoV-2 variants Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.1, BA.4, BA.5, BA.2.75 and BA.2.12.1. The immunity profile was determined for four patient cohorts: pre-pandemic, the first infection in the pandemic, Wuhan(+), and two vaccinated cohorts, the initial double-vaccination with AstraZeneca (AZ) and Pfizer and a final boosted cohort including with known vaccination but unknown mixture of natural infection. A universal protection immunity endotype, U(+), with significant antibody levels to all ten variants was observed in with a incidence of 11% (95% CI 4% - 25%) in the Wuhan(+) cohort challenging directly the ‘one-and-done’ immunity claim. The U(+) incidence rises to 22% (95% CI 12% - 37%) in the double-vaccinated cohort and 54% (95% CI 39% - 68%) in the triple vaccinated cohort. The remaining patients in each cohort show a spectrum of immunity with some drop-out immunity endotypes, U(±), showing poor antibody response to one or more variants. The U(±) incidence in the triple vaccination cohort is 41% (95% CI 28% - 57%) suggesting patients with poor sterilising sera may not clear a SARS-CoV-2 infection leading to viral persistence and mobile microcolonies that may provide a pathophysiology for the symptoms of long Covid. FundingExeter University Alumni, Attomarker Ltd-funded PhD studentship (PJP) at the University of Exeter and Attomarker Ltd funding directly.