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Journal of Virology, April 2009, p. 3810-3815, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.00074-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Replication-Deficient Ebolavirus as a Vaccine Candidate

Peter Halfmann,¹ Hideki Ebihara,^2,3, Andrea Marzi,^3, Yasuko Hatta,¹ Shinji Watanabe,¹ M. Suresh,¹ Gabriele Neumann,¹ Heinz Feldmann,^3,4, and Yoshihiro Kawaoka^1,2,5*

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin,¹ Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan,² Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada,³ Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada,⁴ Institute of Medical Science, University of Tokyo, Tokyo, Japan⁵

Received 12 January 2009/ Accepted 30 January 2009

Ebolavirus causes severe hemorrhagic fever, with case fatality rates as high as 90%. Currently, no licensed vaccine is available against Ebolavirus. We previously generated a replication-deficient, biologically contained Ebolavirus, EbolaVP30, which lacks the essential VP30 gene, grows only in cells stably expressing this gene product, and is genetically stable. Here, we evaluated the vaccine potential of EbolaVP30. First, we demonstrated its safety in STAT-1-knockout mice, a susceptible animal model for Ebolavirus infection. We then tested its protective efficacy in two animal models, mice and guinea pigs. Mice immunized twice with EbolaVP30 were protected from a lethal infection of mouse-adapted Ebolavirus. Virus titers in the serum of vaccinated mice were significantly lower than those in nonvaccinated mice. Protection of mice immunized with EbolaVP30 was associated with a high antibody response to the Ebolavirus glycoprotein and the generation of an Ebolavirus NP-specific CD8⁺ T-cell response. Guinea pigs immunized twice with EbolaVP30 were also protected from a lethal infection of guinea pig-adapted Ebolavirus. Our study demonstrates the potential of the EbolaVP30 virus as a new vaccine platform.

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* Corresponding author. Mailing address: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, 2015 Linden Drive, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail: kawaokay{at}svm.vetmed.wisc.edu

Published ahead of print on 11 February 2009.

Present address: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840.

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Journal of Virology, April 2009, p. 3810-3815, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.00074-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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