Frontiers in Medicine (Jan 2022)

Growth, Antigenicity, and Immunogenicity of SARS-CoV-2 Spike Variants Revealed by a Live rVSV-SARS-CoV-2 Virus

  • Limin S. Ding,
  • Limin S. Ding,
  • Yuhang Zhang,
  • Yuhang Zhang,
  • Dan Wen,
  • Dan Wen,
  • Jianbo Ma,
  • Hao Yuan,
  • Hao Yuan,
  • Hongyue Li,
  • Hongyue Li,
  • Shuguang Duo,
  • Fei Yuan,
  • Yong E. Zhang,
  • Yong E. Zhang,
  • Yong E. Zhang,
  • Aihua Zheng,
  • Aihua Zheng,
  • Aihua Zheng

DOI
https://doi.org/10.3389/fmed.2021.793437
Journal volume & issue
Vol. 8

Abstract

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SARS-CoV-2 is an emerging coronavirus threatening human health and the economy worldwide. As an RNA virus, variants emerge during the pandemic and potentially influence the efficacy of the anti-viral drugs and vaccines. Eight spike variants harboring highly recurrent mutations were selected and introduced into a replication-competent recombinant VSV in place of the original G protein (rVSV-SARS-CoV-2). The resulting mutant viruses displayed similar growth curves in vitro as the wild-type virus and could be neutralized by sera from convalescent COVID-19 patients. Several variants, especially Beta strain, showed resistance to human neutralizing monoclonal antibodies targeting the receptor-binding domain (RBD). A single dose of rVSV-SARS-CoV-2 Beta variant could elicit enhanced and broad-spectrum neutralizing antibody responses in human ACE2 knock-in mice and golden Syrian hamsters, while other mutants generated antibody levels comparable to the wild-type. Therefore, our results will be of value to the development of next-generation vaccines and therapeutic antibodies.

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