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Journal of Virology, October 2006, p. 9659-9666, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00959-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

Kathleen M. Daddario-DiCaprio,1,2,{dagger} Thomas W. Geisbert,1,2,{dagger}* Joan B. Geisbert,1 Ute Ströher,3,4 Lisa E. Hensley,1 Allen Grolla,3 Elizabeth A. Fritz,1 Friederike Feldmann,3 Heinz Feldmann,3,4 and Steven M. Jones3,4,5

Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland,1 Uniformed Services University of the Health Sciences, Bethesda, Maryland,2 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada,3 Department of Medical Microbiology,4 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada5

Received 10 May 2006/ Accepted 12 July 2006

Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients. MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV) expressing the glycoprotein of the Musoke strain of MARV (VSV{Delta}G/MARVGP-Musoke). We used this vaccine to demonstrate complete protection of cynomolgus monkeys against a homologous MARV challenge. While these results are highly encouraging, an effective vaccine would need to confer protection against all relevant strains of MARV. Here, we evaluated the protective efficacy of the VSV{Delta}G/MARVGP-Musoke vaccine against two heterologous MARV strains, the seemingly more pathogenic Angola strain and the more distantly related Ravn strain. In this study, seven cynomolgus monkeys were vaccinated with the VSV{Delta}G/MARVGP-Musoke vector. Three of these animals were challenged with the Angola strain, three with the Ravn strain, and a single animal with the Musoke strain of MARV. Two animals served as controls and were each injected with a nonspecific VSV vector; these controls were challenged with the Angola and Ravn strains, respectively. Both controls succumbed to challenge by day 8. However, none of the specifically vaccinated animals showed any evidence of illness either from the vaccination or from the MARV challenges and all of these animals survived. These data suggest that the VSV{Delta}G/MARVGP-Musoke vaccine should be sufficient to protect against all known MARV strains.


* Corresponding author. Mailing address: USAMRIID, Attn.: MCMR-UIV, 1425 Porter Street, Fort Detrick, MD 21702-5011. Phone: (301) 619-4803. Fax: (301) 619-4627. E-mail: tom.geisbert{at}amedd.army.mil.

{dagger} These authors contributed equally to these studies.


Journal of Virology, October 2006, p. 9659-9666, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00959-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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