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

作者信息

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

机构信息

Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.

出版信息

J Virol. 2017 Aug 10;91(17). doi: 10.1128/JVI.00479-17. Print 2017 Sep 1.


DOI:10.1128/JVI.00479-17
PMID:28615211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5553159/
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. 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.

摘要

相似文献

[1]
Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice.

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[2]
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[3]
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[6]
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[2]
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[3]
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J Med Microbiol. 2021-9

[4]
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[5]
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[6]
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Curr Opin Virol. 2020-10

[7]
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[8]
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Antiviral Res. 2020-1-22

[9]
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[10]
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本文引用的文献

[1]
Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution.

Sci Rep. 2017-4-11

[2]
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Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection.

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Curr Opin Virol. 2016-4

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Methods Mol Biol. 2016

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Sci Transl Med. 2015-12-9

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Recent advances in the development of vaccines for Ebola virus disease.

Virus Res. 2016-1-4

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