A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

Abstract

The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans. Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic. We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform. In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine. We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach. After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus. We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection. The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge. Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine.npj Vaccines (2020) 5:4 ; https://doi.

A complement component C1q-mediated mechanism of antibody-dependent enhancement of Ebola virus infection

“…HEK293 or Vero E6 cells resuspended in phosphate-buffered saline (PBS) were mixed with equal volume of sodium dodecyl sulfate-polyacrylamide (SDS) gel electrophoresis sample buffer containing 2.86 M β-mercaptoethanol (Sigma) and heated to 99 °C for 10 min. SDS-PAGE was performed and separated proteins were transferred to a Trans-Blot polyvinylidene difluoride membrane (Bio-Rad Laboratories) as described elsewhere [ 16 ]. The membrane was blocked for 3 h at room temperature with 3% skim milk.…”

Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis

“…Indeed, an analogous replication-competent recombinant VSV vaccine expressing the Ebola virus (EBOV) glycoprotein protects against lethal EBOV challenge in several animal models (Garbutt et al, 2004;Jones et al, 2005), is safe in immunocompromised nonhuman primates (Geisbert et al, 2008), and was approved for clinical use in humans after successful clinical trials (Henao-Restrepo et al, 2017;Henao-Restrepo et al, 2015). Other live-attenuated recombinant VSV-based vaccines are in pre-clinical development for HIV-1, hantaviruses, filoviruses, arenaviruses, and influenza viruses (Brown et al, 2011;Furuyama et al, 2020;Garbutt et al, 2004;Geisbert et al, 2005;Jones et al, 2005).…”

Development of an Enzyme-Linked Immunosorbent Assay to Determine the Expression Dynamics of Ebola Virus Soluble Glycoprotein during Infection

“…Samples were generated from each EBOV stock produced in Vero E6 cells by mixing a sample 1:1 with SDS gel electrophoresis sample buffer containing 20% β-mercaptoethanol and heated to 99 °C for 10 min. SDS-PAGE and transferred Trans-Blot polyvinylidene difluoride membrane (Bio-Rad Laboratories) with all samples was performed as described elsewhere [ 18 ]. The membrane was blocked for 3 h at room temperature in PBS with 3% powdered milk and 0.05% Tween 20 (Thermo Fisher Scientific).…”