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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift

Tao Li1, Zhimin Cui1,2, Yunfei Jia3,4

  • 1Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, China.

Journal of Medical Virology
|January 15, 2022
PubMed

Insights

Emerging SARS-CoV-2 variants with multiple receptor-binding domain mutations show reduced infectivity but do not cause significant antigenic drift, easing concerns for vaccine development.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • SARS-CoV-2 variants of concern (VOCs) present challenges for infection control.
  • Understanding the impact of mutations on infectivity and antigenicity is crucial for pandemic response.

Purpose of the Study:

  • To assess the infectivity and neutralization of SARS-CoV-2 variants with high-frequency mutations in the receptor-binding domain (RBD).
  • To evaluate the potential for antigenic drift in VOCs with combined RBD mutations.

Main Methods:

  • Construction of pseudoviruses with single or multiple high-frequency amino acid changes in the RBD of Alpha, Beta, and Gamma variants.
  • In vitro infectivity assays using ACE2-overexpressing cells, LLC-MK2, and Vero cells.
  • Neutralization assays using convalescent sera, vaccine sera, and guinea pig immune sera.

Main Results:

  • Single mutations (A520S, V367F, S494P) enhanced infectivity, while multiple mutations reduced it.
  • Specific mutations (E484K, N501Y, K417N, N439K) were associated with reduced efficacy of monoclonal antibodies.
  • Most VOCs showed minimal decrease in neutralizing activity against various human and animal sera, indicating no significant antigenic drift.

Conclusions:

  • Aggregation of multiple RBD mutations in SARS-CoV-2 VOCs does not lead to significant antigenic drift.
  • These findings are valuable for guiding vaccine development strategies against evolving SARS-CoV-2 strains.
Keywords:
SARS-CoV-2cell-cell fusionconvalescent seruminfectivityneutralizationpseudotyped virus

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