Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Highly Protective, Non-infectious Vaccine Against Ebola Virus Challenge
Abstract
An epidemic caused by Ebola virus (EBOV) continues in West Africa, demonstrating the significant public health burden of filovirus infections and highlighting the need for preventive measures to combat the associated disease. Since, no vaccines or antivirals are currently FDA approved, we sought to assess protection conferred by an EBOV vaccine composed of noninfectious vesicular stomatitis virus (VSV) pseudovirions bearing EBOV glycoprotein (GP). A prime/boost vaccination regime protected mice against lethal challenge with mouse-adapted Ebola virus (MA-EBOV) in a dose-dependent manner. As N-linked glycans are thought to shield conserved regions of GP, we also tested if pseudovirions containing GPs lacking N-linked glycans on GP1 would provide effective immunity. High doses of GP/VSV partially or fully denuded of N-linked glycans on GP1 protected mice against MA-EBOV challenge. However, deglycosylated mutants proved less effective than WT GP/VSV at lower doses. Further, neither N-linked glycan deficient GP/VSV provided significant cross protection against Sudan virus. As others have reported, serum from vaccinated mice that were protected against lethal challenge had few to no detectable neutralizing antibodies, indicating that EBOV vaccines do not need to elicit neutralizing antibodies to protect against lethal challenge. A strong correlation was found between the amount of vaccine-induced GP-specific Ig and protection. Our results show that non-infectious GP/VSV pseudovirions serve as a successful vaccination platform, but reduction of the glycan shield is not an effective means of enhancing immunogenicity of EBOV GP. Further, we identify that GP-specific Ig levels provide a good immune correlate of protection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2016
- Accession Number
- AD1004143
Entities
People
- Andrew S Herbert
- Ashley L. Cooney
- Bethany Rhein
- Catherine M. Hunt
- John M Dye
- Katherine J. Perschbacher
- Nicholas J Lennemann
- Rachel Brouillette
- Russell A. Bakken
- Wendy Maury
Organizations
- United States Army Medical Research Institute of Infectious Diseases