An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins

Abstract

Viral glycoproteins mediate entry into host cells, dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus encoding foreign glycoproteins in lieu of its cognate glycoprotein can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of these proteins from viruses requiring high levels of biosafety containment or those lacking efficient infectious clone systems. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant vesicular stomatitis virus encoding foreign glycoproteins. We validate the system using the glycoproteins of different viral families, including numerous SARS-CoV-2 variants and arenaviruses. This described method can facilitate the study of both native vesicular stomatitis virus as well as vesicular stomatitis virus encoding foreign glycoproteins and can serve as the basis for the production of vesicular stomatitis virus-based vaccines.