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Journal of Virology, July 2009, p. 7296-7304, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00561-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus{triangledown}

Thomas W. Geisbert,1,2,3,4,5* Joan B. Geisbert,1,5 Anders Leung,6 Kathleen M. Daddario-DiCaprio,1,4,5 Lisa E. Hensley,5 Allen Grolla,6 and Heinz Feldmann6,7,8

National Emerging Infectious Diseases Laboratories Institute,1 Department of Microbiology,2 Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, Massachusetts,3 Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland,4 Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Maryland,5 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, Canada,6 Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada,7 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th Street, Hamilton, Montana8

Received 18 March 2009/ Accepted 20 April 2009

The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSV{Delta}G/SEBOVGP, VSV{Delta}G/ZEBOVGP, and VSV{Delta}G/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSV{Delta}G/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species.

* Corresponding author. Mailing address: Department of Microbiology, Boston University School of Medicine, 72 East Concord Street, R514, Boston, MA 02118. Phone: (617) 638-4274. Fax: (617) 638-4286. E-mail: geisbert{at}bu.edu

{triangledown} Published ahead of print on 22 April 2009.

Journal of Virology, July 2009, p. 7296-7304, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00561-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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