Snatching the Crown from SARS-CoV-2

Abstract

In this issue of Cell Host & Microbe, three papers describe the pseudotyping of vesicular stomatitis virus (VSV) with the SARS-CoV-2 spike. This VSV-CoV-2-S platform allows virus neutralization assays to be performed at BSL-2 and also has applications as a candidate vectored vaccine to elicit protective immunity against SARS-CoV-2.

Figure 1

Development of a Replication-Competent VSV Vector Pseudotyped with SARS-CoV-2 S Glycoprotein as a Serological Tool and Vaccine Candidate (A) Schematic diagram of the SARS-CoV-2 coronavirus, highlighting the S surface glycoprotein, which is a major target for vaccine development. Structure shown for S is PDB ID: 6XKL (PMID: 32577660). (B) Schematic diagram of the bullet-shaped VSV, with major viral proteins highlighted. (C) Schematic diagram showing the structure of VSV when successfully pseudotyped with the SARS-CoV-2 S glycoprotein (VSV-SARS-CoV-2-S_Δ21). (D) In manuscripts by Case and Dieterle (Case et al., 2020b; Dieterle et al., 2020), the authors demonstrate that VSV-SARS-CoV-2-S_Δ21 expressing enhanced green fluorescent protein (eGFP) as a reporter transgene, bearing SARS-CoV-2 S on the surface, can be used as a serological tool to measure NAbs to SARS-CoV-2 in a manner comparable to neutralization assays performed at BSL-3 with SARS-CoV-2 virus. (E) In a separate manuscript, Case and colleagues show that VSV-SARS-CoV-2-S_Δ21 can also be used as an immunogenic vaccine against SARS-CoV-2, eliciting antibody responses against S and its RBD, as well as NAbs (Case et al., 2020a). (F) By using a previously established model to sensitize mice to challenge with SARS-CoV-2 by pre-administering a non-replicating adenoviral vector expressing human ACE2 (Hassan et al., 2020), the authors showed that immunization with VSV-SARS-CoV-2-S_Δ21, or passive transfer of sera from VSV-SARS-CoV-2-S_Δ21-immunized mice, could protect mice from SARS-CoV-2 challenge. Figures were created with BioRender.