TY - JOUR

T1 - The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization

AU - Bayarri-Olmos, Rafael

AU - Rosbjerg, Anne

AU - Johnsen, Laust Bruun

AU - Helgstrand, Charlotte

AU - Bak-Thomsen, Theresa

AU - Garred, Peter

AU - Skjoedt, Mikkel Ole

N1 - Funding Information: supported by grants from the Carlsberg Foundation (CF20-0045 to M.-O .S., R. B.-O., and P. G.) and the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201 to M.-O. S., R. B.-O., and P. G.). Publisher Copyright: © 2021 THE AUTHORS.

PY - 2021

Y1 - 2021

N2 - Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 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 angiotensin-converting enzyme-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals or 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 angiotensin-converting enzyme-2 receptor with a 4-fold higher affinity than the original strain, suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in the frequency of the clusterfive variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses.

AB - Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 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 angiotensin-converting enzyme-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals or 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 angiotensin-converting enzyme-2 receptor with a 4-fold higher affinity than the original strain, suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in the frequency of the clusterfive variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses.

U2 - 10.1016/j.jbc.2021.100536

DO - 10.1016/j.jbc.2021.100536

M3 - Journal article

C2 - 33716040

AN - SCOPUS:85104593446

VL - 296

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

M1 - A13

ER -