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Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses

Nature Medicine volume 11, pages 786790 (2005) | Download Citation

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Abstract

Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein. A single intramuscular injection of the EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges. Notably, vaccine vector shedding was not detectable in the monkeys and none of the animals developed fever or other symptoms of illness associated with vaccination. The EBOV vaccine induced humoral and apparent cellular immune responses in all vaccinated monkeys, whereas the MARV vaccine induced a stronger humoral than cellular immune response. No evidence of EBOV or MARV replication was detected in any of the protected animals after challenge. Our data suggest that these vaccine candidates are safe and highly efficacious in a relevant animal model.

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Acknowledgements

The authors thank D. Braun, D. Dick, F. Feldmann and C. Rice for technical assistance and assistance with animal care. We are grateful to G. Nabel, US National Institutes of Health Vaccine Research Center, for support and discussions. The study was supported by a grant from the Canadian Institute of Health Research (CIHR – MOP – 43921) awarded to H.F., Health Canada. The study was supported in part by the Medical Chemical/Biological Defense Research Program, US Army Medical Research and Material Command (project number 04-4-7J-012). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Army.

Author information

Author notes

    • Steven M Jones
    •  & Heinz Feldmann

    These authors contributed equally to this work.

Affiliations

  1. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada.

    • Steven M Jones
    • , Heinz Feldmann
    • , Ute Ströher
    • , Lisa Fernando
    •  & Allen Grolla
  2. Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 3R2, Canada.

    • Steven M Jones
  3. Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 3R2, Canada.

    • Heinz Feldmann
    •  & Ute Ströher
  4. United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Maryland 21702, USA.

    • Joan B Geisbert
    • , Elizabeth A Fritz
    • , Lisa E Hensley
    • , Peter B Jahrling
    •  & Thomas W Geisbert
  5. Institute of Virology, Philipps-University, Robert Koch Str. 17, 35037, Marburg, Germany.

    • Hans-Dieter Klenk
  6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Covent Drive, Bethesda, Maryland, USA.

    • Nancy J Sullivan
  7. Filovirus Laboratory, University Claude Bernard Lyon-1, INSERM U412, 69007 Lyon, France.

    • Viktor E Volchkov
  8. Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA.

    • Kathleen M Daddario

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Heinz Feldmann.

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DOI

https://doi.org/10.1038/nm1258

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