Vaccine, Booster and Natural Antibody Binding to SARS-CoV-2 Omicron (BA.1) Spike Protein and Vaccine Efficacy (preprint)

ABSTRACT

The SARS-CoV-2 Omicron variant (BA.1) has 25 unique mutations to the Spike glycoprotein, suggesting the efficacy of current vaccines against the new variant may be seriously degraded. A fully quantitative antibody binding study was performed for Spike Omicron (SO) and original Spike (S) proteins simultaneously on three cohorts of patients convalescent following RT-PCR-confirmed infection in early 2020, double-vaccinated at [≥]2 weeks, and vaccine boosters. The average (mode) of the booster cohort response distributions were 15.1 mg/L and 13.4 mg/L for S and SO, respectively, compared with the significantly lower double-vaccinated average, S=2.4 mg/L, SO=2.0 mg/L, and natural infections average S=2.0 mg/L, SO = 1.8 mg/L. A preliminary epitope degradation screen was performed for a panel of antibodies raised to the S1 and S2 regions of the original S protein. The panel showed significant degradation to antibody epitopes in the S1 region. Differential antibody binding of the vaccine response to S and SO suggests vaccine efficacy may be reduced by up to 50% against the Omicron variant.