Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents

Gary Wong; Jonathan Audet; Lisa Fernando; Hugues Fausther-Bovendo; Judie B Alimonti; Gary P Kobinger; Xiangguo Qiu

doi:10.1016/j.vaccine.2014.08.028

Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents

Vaccine. 2014 Sep 29;32(43):5722-9. doi: 10.1016/j.vaccine.2014.08.028. Epub 2014 Aug 27.

Authors

Gary Wong¹, Jonathan Audet¹, Lisa Fernando², Hugues Fausther-Bovendo², Judie B Alimonti², Gary P Kobinger³, Xiangguo Qiu⁴

Affiliations

¹ Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2 Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
² Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2 Canada.
³ Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2 Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada; Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
⁴ Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2 Canada. Electronic address: xiangguo.qiu@phac-aspc.gc.ca.

Abstract

Ebola virus (EBOV) infections cause lethal hemorrhagic fever in humans, resulting in up to 90% mortality. EBOV outbreaks are sporadic and unpredictable in nature; therefore, a vaccine that is able to provide durable immunity is needed to protect those who are at risk of exposure to the virus. This study assesses the long-term efficacy of the vesicular stomatitis virus (VSV)-based vaccine (VSVΔG/EBOVGP) in two rodent models of EBOV infection. Mice and guinea pigs were first immunized with 2×10(4) or 2×10(5) plaque forming units (PFU) of VSVΔG/EBOVGP, respectively. Challenge of mice with a lethal dose of mouse-adapted EBOV (MA-EBOV) at 6.5 and 9 months after vaccination provided complete protection, and 80% (12 of 15 survivors) protection at 12 months after vaccination. Challenge of guinea pigs with a lethal dose of guinea pig-adapted EBOV (GA-EBOV) at 7, 12 and 18 months after vaccination resulted in 83% (5 of 6 survivors) at 7 months after vaccination, and 100% survival at 12 and 18 months after vaccination. No weight loss or clinical signs were observed in the surviving animals. Antibody responses were analyzed using sera from individual rodents. Levels of EBOV glycoprotein-specific IgG antibody measured immediately before challenge appeared to correlate with protection. These studies confirm that vaccination with VSVΔG/EBOVGP is able to confer long-term protection against Ebola infection in mice and guinea pigs, and support follow-up studies in non-human primates.

Keywords: Ebola; Guinea pig, Mouse; Long-term immunity; Vaccine; Vesicular stomatitis virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral / blood
Antibody Formation
Ebola Vaccines / immunology*
Ebolavirus
Female
Guinea Pigs
Hemorrhagic Fever, Ebola / prevention & control*
Immunoglobulin G / blood
Mice, Inbred BALB C
Vesiculovirus / immunology*
Viral Envelope Proteins / immunology*

Substances

Antibodies, Viral
Ebola Vaccines
Immunoglobulin G
Viral Envelope Proteins
envelope glycoprotein, Ebola virus

Grants and funding

Canadian Institutes of Health Research/Canada