Abstract

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.

Highlights

  • COVID-19 is a highly transmissible and life-threatening disease that emerged in December 2019

  • To study the emerging variants of SARS-CoV-2 during the pandemic, we collected 24,743 SARS-CoV-2 sequences reported in the Global Initiative for Sharing All Influenza Data (GISAID) database on May 21, 2020 and compared them with the reference Wuhan-Hu-1 stain (MN_908947)

  • The most dominant variant carries the D614G mutation, which is located outside the receptor-binding domain (RBD) of the S1 subunit

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Summary

Introduction

COVID-19 is a highly transmissible and life-threatening disease that emerged in December 2019. As of September 2021, more than 223 million confirmed cases and 4.6 million deaths were reported worldwide by WHO. The etiological agent of COVID-19, SARS-CoV-2, causes symptoms ranging from mild to lethal pneumonia and even multiple organ failure [1, 2]. The genome of SARS-CoV-2 encodes four structural proteins, including spike (S), envelope (E), matrix (M), and nucleocapsid (N) [3]. S protein is the major glycoprotein on the surface of SARS-CoV-2 and is responsible for receptor binding and membrane fusion [4, 5]. S protein is processed by the host’s furin protease into S1 and S2 [6].

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