Effect of SARS-CoV-2 (Y453F) variant on COVID-19 vaccine

Mustelidae animals such as mink and ferrets can be infected with SARS-CoV-2 relatively easily compared to other mammals. It is not clear why SARS-CoV-2 is so contagious to these animals (1). It is clear that when SARS-CoV-2 is infected with farmed minks that is kept in large quantities in a high density environment, SARS-CoV-2 proliferates in large quantities in the mink body. As a result, humans may pose a high risk of infection with SARS-CoV-2 as well as farmed minks.

Natural selection “adaptation” in the coronavirus can occur during coronavirus amplification in vivo in farmed mink (2). Natural selection in such viruses is observed by the appearance of mutations in SARS-CoV-2 that are not observed during the growth process in humans (2,3). Infection with a mutant (Y453F) of SARS-CoV-2 from farmed mink is widespread among people (4).

Recent studies have revealed the following matters (5).
The Y453F mutation does not affect the three-dimensional structure of conventional SARS-CoV-2 spike glycoproteins. It was clarified that the binding property of the spike glycoprotein Y453F mutant to human ACE2 was slightly weaker than that of the conventional SARS-CoV-2 spike glycoprotein. It was revealed that the affinity between the spike glycoprotein Y453F mutant and 4 of the 6 neutralizing antibodies examined was clearly weak compared to the conventional SARS-CoV-2 spike glycoprotein.

It is considered that the affinity between the appropriate amino acid residues in the variable region of the antibody and the spike glycoprotein RBD F453 has diminished as cause of weak recognition of monoclonal antibodies for spike glycoproteins. Subspecies of SARS-CoV-2 derived from farmed mink has been observed example of infected peoples, the virus mutants are inherited by infected individuals.

Since the mutations have occurred in the SARS-CoV-2, subspecies of SARS-CoV-2, which are susceptible to human and animal infection, easily propagate in the host. The spread of SARS-CoV-2 variants mediated by millions of farmed minks is uncontrolled. As a result, there is concern that SARS-CoV-2 mutants, which cause serious symptoms in humans, may be spread all over the world.

Acknowledgments
We thank all the medical staffs and co-medical staffs for providing and helping medical research at National Hospital Organization Kyoto Medical Center.

Reference
1. Enserink M. Science 368(6496): 1169 (2020)
2. Oude Munnink BB. et al. Science DOI: 10.1126/science.abe5901
3. Hayashi T. Konishi I. Science https://science.sciencemag.org/content/368/6496/1169/tab-e-letters
4. Mallapaty S. Nature 587(7834): 340-341 (2020).
5. Hayashi T. et al. bioRxiv Cold Spring Harbor https://www.biorxiv.org/content/10.1101/2020.11.27.401893v1

JAMA Published on January 2021 by Kyoto@Takuma H