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

Nicholas J Lennemann; Andrew S Herbert; Rachel Brouillette; Bethany Rhein; Russell A Bakken; Katherine J Perschbacher; Ashley L Cooney; Catherine L Miller-Hunt; Patrick Ten Eyck; Julia Biggins; Gene Olinger; John M Dye; Wendy Maury

doi:10.1128/JVI.00479-17

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

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

Nicholas J Lennemann, Andrew S Herbert, Rachel Brouillette, Bethany Rhein, Russell A Bakken, Katherine J Perschbacher, Ashley L Cooney, Catherine L Miller-Hunt, Patrick Ten Eyck, Julia Biggins, …

Journal of virology, Vol.91(17), e00479-17

09/01/2017

DOI: 10.1128/JVI.00479-17

PMCID: PMC5553159

PMID: 28615211

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Abstract

The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success. IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

Ebola Virus

filovirus

glycoproteins

glycosylation

pseudovirion

Spotlight

vaccine

Vaccines and Antiviral Agents

Details

Title: Subtitle: Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice
Creators: Nicholas J Lennemann - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Andrew S Herbert - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Rachel Brouillette - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Bethany Rhein - University of Iowa
Russell A Bakken - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Katherine J Perschbacher - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Ashley L Cooney - University of Iowa, Stead Family Department of Pediatrics
Catherine L Miller-Hunt - University of Iowa
Patrick Ten Eyck - University of Iowa, Biostatistics
Julia Biggins - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Gene Olinger - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
John M Dye - Medical Research Institute
Wendy Maury - University of Iowa, Microbiology and Immunology
Resource Type: Journal article
Publication Details: Journal of virology, Vol.91(17), e00479-17
DOI: 10.1128/JVI.00479-17
PMID: 28615211
PMCID: PMC5553159
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Grant note: T32 AI007533 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01 AI77519 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32 AI996343 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) CB3947 / U.S. Department of Defense (DOD)
Alternative title: VSV Pseudovirion Vaccine against Ebola Virus
Language: English
Date published: 09/01/2017
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Biostatistics
Record Identifier: 9984210509302771

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