The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization

Bayarri-Olmos, Rafael; Rosbjerg, Anne; Johnsen, Laust Bruun; Helgstrand, Charlotte; Bak-Thomsen, Theresa; Garred, Peter; Skjoedt, Mikkel-Ole

SARS-CoV-2 transmission from humans to animals has been reported for many domesticated species, including farmed minks. The identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. One genetic variant, known as “cluster-five”, arose among farmed minks in Denmark and resulted in a complete shutdown of the world’s largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the cluster-five variant, which contains a mutation resulting in a Y453F residue change in the receptor-binding domain (RBD) of the spike protein. Using an ELISA-based ACE-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals nor affect the neutralizing antibody response in a vaccine mouse model based on the original Wuhan strain RBD or spike as antigens. However, biolayer interferometry analysis demonstrates that it binds the human ACE-2 receptor with a four-fold higher affinity compared to the original strain suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in frequency of the cluster-five variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses.