close
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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

Nature Medicine volume 11, pages 786–790 (2005) Cite this article

Save article
View saved research

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.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Immunization, challenge and rechallenge of nonhuman primates.
Figure 2: Viremia levels in nonhuman primates after immunization and challenge.
Figure 3: Humoral immune response in nonhuman primates to ZEBOV and MARV before and after challenge.
Figure 4: Cellular immune response in nonhuman primates before and after challenge with ZEBOV.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Sanchez, A. et al. Filoviridae: Marburg and Ebola Viruses. in Fields Virology (eds. Knipe, D.M. & Howley, P.M.) 1279–1304 (Lippincott Williams & Wilkins, Philadelphia, 2001).

    Google Scholar 

  2. Feldmann, H., Jones, S., Klenk, H.D. & Schnittler, H.J. Ebola virus: from discovery to vaccine. Nat. Rev. Immunol. 3, 677–685 (2003).

    Article  CAS  Google Scholar 

  3. Geisbert, T.W. & Jahrling, P.B. Exotic emerging viral diseases: progress and challenges. Nat. Med. 10 suppl. 12 Suppl, S110–S121 (2004).

    Article  CAS  Google Scholar 

  4. Centers for Disease Control and Prevention (CDC). Outbreak of Marburg virus hemorrhagic fever–Angola, October 1, 2004-March 29, 2005. MMWR Morb. Mortal. Wkly. Rep. 54, 308–309 (2005).

  5. Borio, L. et al. Hemorrhagic fever viruses as biological weapons: medical and public health management. J. Am. Med. Assoc. 287, 2391–2405 (2002).

    Article  Google Scholar 

  6. Garbutt, M. et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J. Virol. 78, 5458–5465 (2004).

    Article  CAS  Google Scholar 

  7. Geisbert, T.W. et al. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg. Infect. Dis. 8, 503–507 (2002).

    Article  Google Scholar 

  8. Geisbert, T.W. & Jahrling, P.B. Towards a vaccine against Ebola virus. Expert Rev. Vaccines 2, 777–789 (2003).

    Article  Google Scholar 

  9. Sullivan, N.J., Sanchez, A., Rollin, P.E., Yang, Z.Y. & Nabel, G.J. Development of a preventive vaccine for Ebola virus infection in primates. Nature 408, 605–609 (2000).

    Article  CAS  Google Scholar 

  10. Sullivan, N.J. et al. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 424, 681–684 (2003).

    Article  CAS  Google Scholar 

  11. Brandt, C.D. et al. Infections in 18,000 infants and children in a controlled study of respiratory tract disease. I. Adenovirus pathogenicity in relation to serologic type and illness syndrome. Am. J. Epidemiol. 90, 484–500 (1969).

    Article  CAS  Google Scholar 

  12. Piedra, P.A., Poveda, G.A., Ramsey, B., McCoy, K. & Hiatt, P.W. Incidence and prevalence of neutralizing antibodies to the common adenoviruses in children with cystic fibrosis: implication for gene therapy with adenovirus vectors. Pediatrics 101, 1013–1019 (1998).

    Article  CAS  Google Scholar 

  13. Schulick, A.H. et al. Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity. J. Clin. Invest. 99, 209–219 (1997).

    Article  CAS  Google Scholar 

  14. Hevey, M., Negley, D., Pushko, P., Smith, J. & Schmaljohn, A. Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology 251, 28–37 (1998).

    Article  CAS  Google Scholar 

  15. Roberts, A., Buonocore, L., Price, R., Forman, J. & Rose, J.K. Attenuated vesicular stomatitis viruses as vaccine vectors. J. Virol. 73, 3723–3732 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Roberts, A. et al. Vaccination with a recombinant vesicular stomatitis virus expressing an influenza virus hemagglutinin provides complete protection from influenza virus challenge. J. Virol. 72, 4704–4711 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Schlereth, B., Rose, J.K., Buonocore, L., ter Meulen, V. & Niewiesk, S. Successful vaccine-induced seroconversion by single-dose immunization in the presence of measles virus-specific maternal antibodies. J. Virol. 74, 4652–4657 (2000).

    Article  CAS  Google Scholar 

  18. Rose, N.F. et al. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell 106, 539–549 (2001).

    Article  CAS  Google Scholar 

  19. Wagner, R.R. & Rose, J.K. Rhabdoviridae: The Viruses And Their Replication. in Fields Virology, Vol. 1 (eds. Knipe, D.M. & Howley, P.M.) (Lippincott Williams & Wilkins, Philadelphia, 1996).

    Google Scholar 

  20. Sanchez, A., Trappier, S.G., Mahy, B.W., Peters, C.J. & Nichol, S.T. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc. Natl Acad. Sci. USA 93, 3602–3607 (1996).

    Article  CAS  Google Scholar 

  21. Bukreyev, A.A., Volchkov, V.E., Blinov, V.M., Dryga, S.A. & Netesov, S.V. The complete nucleotide sequence of the Popp (1967) strain of Marburg virus: a comparison with the Musoke (1980) strain. Arch. Virol. 140, 1589–1600 (1995).

    Article  CAS  Google Scholar 

  22. Ignatyev, G.M., Agafonov, A.P., Streltsova, M.A. & Kashentseva, E.A. Inactivated Marburg virus elicits a nonprotective immune response in Rhesus monkeys. J. Biotechnol. 44, 111–118 (1996).

    Article  CAS  Google Scholar 

  23. Schnell, M.J., Buonocore, L., Kretzschmar, E., Johnson, E. & Rose, J.K. Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are incorporated efficiently into virus particles. Proc. Natl Acad. Sci. USA 93, 11359–11365 (1996).

    Article  CAS  Google Scholar 

  24. Jahrling, P.B. et al. Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J. Infect. Dis. 179 Suppl 1, S224–S234 (1999).

    Article  CAS  Google Scholar 

  25. Sanchez, A. et al. Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J. Virol. 78, 10370–10377 (2004).

    Article  CAS  Google Scholar 

  26. Smith, D.H. et al. Marburg-virus disease in Kenya. Lancet 1, 816–820 (1982).

    Article  CAS  Google Scholar 

  27. Jahrling, P.B. Filoviruses and Arenaviruses. in Manual of Clinical Microbiology (ed. Murray, P.R.) 1125–1136 (ASM Press, Washington, DC, 1999).

    Google Scholar 

Download references

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

  1. Steven M Jones and Heinz Feldmann: These authors contributed equally to this work.

Authors and Affiliations

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

    Steven M Jones, Heinz Feldmann, Ute Ströher, Lisa Fernando & Allen Grolla

  2. Department of Immunology, University of Manitoba, Winnipeg, R3E 3R2, Manitoba, Canada

    Steven M Jones

  3. Department of Medical Microbiology, University of Manitoba, Winnipeg, R3E 3R2, Manitoba, Canada

    Heinz Feldmann & Ute Ströher

  4. United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, 21702, Maryland, 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, Marburg, 35037, 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, Lyon, 69007, France

    Viktor E Volchkov

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

    Kathleen M Daddario

Authors
  1. Steven M Jones
    View author publications

    Search author on:PubMed Google Scholar

  2. Heinz Feldmann
    View author publications

    Search author on:PubMed Google Scholar

  3. Ute Ströher
    View author publications

    Search author on:PubMed Google Scholar

  4. Joan B Geisbert
    View author publications

    Search author on:PubMed Google Scholar

  5. Lisa Fernando
    View author publications

    Search author on:PubMed Google Scholar

  6. Allen Grolla
    View author publications

    Search author on:PubMed Google Scholar

  7. Hans-Dieter Klenk
    View author publications

    Search author on:PubMed Google Scholar

  8. Nancy J Sullivan
    View author publications

    Search author on:PubMed Google Scholar

  9. Viktor E Volchkov
    View author publications

    Search author on:PubMed Google Scholar

  10. Elizabeth A Fritz
    View author publications

    Search author on:PubMed Google Scholar

  11. Kathleen M Daddario
    View author publications

    Search author on:PubMed Google Scholar

  12. Lisa E Hensley
    View author publications

    Search author on:PubMed Google Scholar

  13. Peter B Jahrling
    View author publications

    Search author on:PubMed Google Scholar

  14. Thomas W Geisbert
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Heinz Feldmann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, S., Feldmann, H., Ströher, U. et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 11, 786–790 (2005). https://doi.org/10.1038/nm1258

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nm1258

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing