Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

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Acknowledgements

We thank M. Cichanowski for graphics, A. Tislerics and B. Hartman for assistance with the manuscript and R. Seder for review and helpful suggestions. S. Perfetto and S. Norris and D. Follmann for technical discussions, and the Vaccine Research Center's Nonhuman Primate Immunogenicity Core for NHP sample processing. We thank the Vaccine Research Center Laboratory Animal Medicine, S. Rao, A. Taylor, J.P. Todd and H. Bao for protocol support and the NIH Division of Veterinary Resources for animal care. We also thank H. Esham for technical assistance and data management and D. Alves for pathology assistance. TPG shuttle vector was provided by A. Siccardi (Istituto San Raffaele). This work was supported by the Intramural Research Program of the US NIH NIAID Vaccine Research Center. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Army or the US Department of Defense.

Author information

Author notes

    • Anna N Honko
    • , Joshua C Johnson
    • , Lisa Hensley
    •  & Gary J Nabel

    Present addresses: Integrated Research Facility, NIAID, NIH, Fort Detrick, Maryland, USA (A.N.H., J.C.J. and L.H.), and Sanofi, Cambridge, Massachusetts, USA (G.J.N.).

    • Clement Asiedu

    Deceased.

Affiliations

  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.

    • Daphne A Stanley
    • , Clement Asiedu
    • , Annie W Lau-Kilby
    • , Kathryn E Foulds
    • , Cheng Cheng
    • , Lingshu Wang
    • , Mitzi M Donaldson
    • , Mario Roederer
    • , Gary J Nabel
    • , John Mascola
    • , Richard A Koup
    •  & Nancy J Sullivan
  2. United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.

    • Anna N Honko
    • , John C Trefry
    • , Joshua C Johnson
    •  & Lisa Hensley
  3. Okairos, Rome, Italy.

    • Virginia Ammendola
    • , Adele Abbate
    • , Fabiana Grazioli
    • , Stefano Colloca
    • , Antonella Folgori
    •  & Alfredo Nicosia
  4. Centro Ingegneria Genetica (CEINGE), Naples, Italy.

    • Alfredo Nicosia
  5. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.

    • Alfredo Nicosia
  6. Keires AG, Basel, Switzerland.

    • Riccardo Cortese

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Contributions

D.A.S., C.A., G.J.N., J.M., R.A.K. and N.J.S. designed these studies. D.A.S., A.N.H., C.A., J.C.T. and N.J.S. wrote animal study protocols and executed in vivo studies. D.A.S., C.A., A.W.L.-K., K.E.F., M.M.D. and M.R. conducted immune assessments. A.N.H., J.C.T., J.C.J. and L.H. executed challenge studies and performed post-challenge assays. V.A., A.A., F.G., C.C. and L.W. constructed, produced and characterized vectors. S.C., A.F., A.N. and R.C. identified chimp adenoviruses.

Competing interests

N.J.S., G.J.N., S.C., A.F., A.N. and R.C. claim intellectual property on gene-based vaccines for ebolavirus. S. C. and A.N. are named inventors in patents issued in the US Patent and Trademark Office and European, Australian, Chinese, Indian,and Japanese Patent Offices, and pending in the Canadian and Hong Kong Patent Offices, on chimpanzee adenovirus 3 (ChAd3). S. C., A.N, V.A. and R.C. are named inventors in a patent application with patents pending with the US Patent and Trademark Office and European Patent Office on filovirus vaccine.

Corresponding author

Correspondence to Nancy J Sullivan.

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DOI

https://doi.org/10.1038/nm.3702

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