Single-Vector, Single-Injection Recombinant Vesicular Stomatitis Virus Vaccines Against High-Containment Viruses

Abstract

There are many avenues for making an effective vaccine against viruses. Depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (VSV). VSV is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate to high titers in a wide variety of mammalian and insect cells. The use of reverse genetics to recover infectious and single-cycle replicating VSV from plasmid DNA transfected in cell culture began a revolution in the study of recombinant VSV (rVSV). This platform can be manipulated to study the viral genetic sequences and proteins important in the virus life cycle. Additionally, foreign genes can be inserted between naturally occurring or generated start/stop signals and polyadenylation sites within the VSV genome. VSV has a tolerance for foreign gene expression which has led to numerous rVSVs reported in the literature. Of particular interest are the very effective single-dose rVSV vaccine vectors against high-containment viruses such as filoviruses, henipaviruses, and arenaviruses. Herein we describe the methods for selecting foreign antigenic genes, selecting the location within the VSV genome for insertion, generation of rVSV using reverse genetics, and proper vaccine study designs.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

“…This stands in contrast to findings with virus-like particles, where protection in mice against lethal filovirus challenge requires either a regimen of a prime and two boosts or the presence of adjuvants (9, 42, 50-52). VSVΔG SRIPs bearing the glycoprotein from other highly pathogenic viruses such as Nipah virus have also been demonstrated to serve as a protective vaccine (53,54). It is thought that one or more VSV proteins have adjuvant-like properties, thereby eliciting robust adaptive immune responses to the vaccine immunogen (21,55,56), although which VSV protein(s) is important for this enhancing effect has not been identified.…”

The family Rhabdoviridae: mono- and bipartite negative-sense RNA viruses with diverse genome organization and common evolutionary origins

“…next generation sequencing, metagenomics), reverse genetics of the prototype vesiculoviruses (Schnell et al, 1994; Whelan et al, 1995) allowed exploration of rhabdovirus plasticity and evolution at the genetic level, as well as an understanding of the factors influencing gene expression and molecular and cellular basis of pathogenesis, and their use as vaccine delivery vehicles (reviewed in: Whitt et al, 2016). The error-prone nature of their RNA-dependent RNA polymerase results in the generation of a rich diversity of genetic variants following each replication cycle, which are subject to adaptation due to selective pressures under different conditions, such as alternative hosts (vector vs vertebrate) during the course of their natural transmission (Novella et al, 2010; Novella et al, 2011; Wasik et al, 2016).…”

Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins

“…A reverse genetics system for VSV has been previously Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific REPORTS | 7: 11607 | Envelope proteins of different virus species can be incorporated into VSV particles, even when they are provided in trans, generating pseudotype VSVs. Pseudotype VSVs enter cells through receptor binding and membrane fusion mediated by incorporated envelope proteins of different viruses, and the entry can be traced with reporter gene expression in the recombinant VSV genome [15][16][17] .In the present study, various human cell lines were tested for their susceptibility (defined as the capacity for viral entry) to RV using a recombinant VSV pseudotyped with RV proteins.…”