SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization

Area of Science:

• Virology
• Immunology
• Public Health

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between humans and farmed mink has been documented.
• Viral variants with mutations in the spike (S) protein emerged in mink and were transmitted back to humans, raising public health concerns.

Purpose of the Study:

• To investigate the functional impact of SARS-CoV-2 mutations found in mink on viral entry into human cells.
• To assess the susceptibility of mink-associated SARS-CoV-2 variants to neutralization by antibodies, including therapeutic antibodies and those from COVID-19 patients.

Main Methods:

• In vitro analysis of SARS-CoV-2 variant entry into human cells.
• Assessment of neutralization by soluble angiotensin-converting enzyme 2 (ACE2).
• Evaluation of neutralization by a specific antibody and sera/plasma from coronavirus disease 2019 (COVID-19) patients.

Main Results:

• Mutations common in mink-derived SARS-CoV-2 are largely compatible with efficient human cell entry.
• The Y453F mutation significantly reduces neutralization by a therapeutic antibody and COVID-19 patient sera.
• Soluble ACE2 effectively inhibited viral entry, indicating conserved interaction mechanisms.

Conclusions:

• SARS-CoV-2 variants from mink possess mutations that facilitate human cell entry.
• Antibody responses from infection or certain COVID-19 therapies may provide inadequate protection against these mink-associated variants.
• The Y453F mutation highlights a potential mechanism for immune evasion by SARS-CoV-2 variants originating in mink.