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Development of a preventive vaccine for Ebola virus infection in primates

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Abstract

Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date1,2. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates.

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Figure 1: Ebola-specific antibody responses generated by different DNA/adenovirus prime-boost combinations.
Figure 2: DNA-adenovirus immunization of cynomolgus macaques.
Figure 3: Protection of cynomolgus macaques against lethal challenge with Ebola virus after DNA-adenovirus immunization.

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Acknowledgements

We thank J. DeCoster and R. Grecoe for technical assistance with primates and G. Reynolds for the animal handling in the Biosafety Laboratory-4, K. Reiman and J. Stein for advice, assistance and comments, and N. Barrett, C. Davis and A. Tislerics for help in preparing the manuscript.

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Authors and Affiliations

  1. Vaccine Research Center, National Institutes of Health, 40 Convent Drive, MSC-3005, Bethesda, 20892, Maryland, USA

    Nancy J. Sullivan, Zhi-yong Yang & Gary J. Nabel

  2. Special Pathogens Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G14, Atlanta, 30333, Georgia, USA

    Anthony Sanchez & Pierre E. Rollin

Authors
  1. Nancy J. Sullivan
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  2. Anthony Sanchez
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  3. Pierre E. Rollin
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  4. Zhi-yong Yang
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  5. Gary J. Nabel
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Corresponding author

Correspondence to Gary J. Nabel.

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Sullivan, N., Sanchez, A., Rollin, P. et al. Development of a preventive vaccine for Ebola virus infection in primates. Nature 408, 605–609 (2000). https://doi.org/10.1038/35046108

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  • DOI: https://doi.org/10.1038/35046108

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