Quantitative epitope analysis reveals drastic 63% reduced immuno-affinity and 60% enhanced transmissibility for SARS-CoV-2 variants.

SARS-CoV-2 is the cause of a global pandemic that has led to more than 4 million deaths, continues to spread and holds the world in a tight grip. The virus has developed substantial mutations that undermine the efficacy of current vaccines and monoclonal antibody therapies. Semi-quantitative immuno - and neutralization assays are unable to provide direct quantitative insights about the minute variations of emerging mutants. Here, we develop a quantitative assay that enables synchronous screening of emerging variant epitopes with single amino acid resolution. We report on specific label-free quantitative nanomechanical analysis of pseudovirus spike interaction with ACE2 receptors. Within minutes, we can characterize the B.1.1.7 variant transmissibility due to its 63% increased binding, and measure a 60% reduced efficacy of antibodies towards B.1.351 and P.1 variants. Our technology can assist vaccine development studies, with focus on comparing protection patterns and novel vaccine candidates and tracking of immunity over time.