This Article Full Text (PDF) Other Versions of this Article: CVI.00162-06v1 13/11/1267    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martin, J. E. Search for Related Content PubMed PubMed Citation Articles by Martin, J. E.

 Previous Article  |  Next Article 

Clin. Vaccine Immunol. doi:10.1128/CVI.00162-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A DNA Vaccine for Ebola Virus is Safe and Immunogenic in a Phase I Clinical Trial

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, Maryland 20892-3017; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024

^* To whom correspondence should be addressed. Email: bgraham{at}nih.gov,

	Abstract

Background: Ebola viruses represent a class of filoviruses that cause severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola vaccine in its first Phase I human study.

Methods: A 3-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from Zaire and Sudan/Gulu species, as well as the nucleoprotein, was evaluated in a randomized, placebo-controlled, double-blinded, dose-escalation study. Healthy adults, ages 18-44 years, were randomized to receive three injections of vaccine at 2 mg (n=5), 4 mg (n=8), 8 mg (n=8), or placebo (n=6). Immunogenicity was assessed by ELISA, IP-Western blot, intracellular cytokine staining (ICS) and ELISpot.

Results: The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody response to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4⁺ T cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8⁺ T cell GP-specific responses were detected by ICS assay in 6/20 vaccinees.

Conclusions: This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from non-human primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.

This article has been cited by other articles:

• Bansal, A., Jackson, B., West, K., Wang, S., Lu, S., Kennedy, J. S., Goepfert, P. A. (2008). Multifunctional T-Cell Characteristics Induced by a Polyvalent DNA Prime/Protein Boost Human Immunodeficiency Virus Type 1 Vaccine Regimen Given to Healthy Adults Are Dependent on the Route and Dose of Administration. J. Virol. 82: 6458-6469 [Abstract] [Full Text]  
• Liang, R., van den Hurk, J. V., Landi, A., Lawman, Z., Deregt, D., Townsend, H., Babiuk, L. A., van Drunen Littel-van den Hurk, S. (2008). DNA prime protein boost strategies protect cattle from bovine viral diarrhea virus type 2 challenge. J. Gen. Virol. 89: 453-466 [Abstract] [Full Text]  
• Bukreyev, A., Rollin, P. E., Tate, M. K., Yang, L., Zaki, S. R., Shieh, W.-J., Murphy, B. R., Collins, P. L., Sanchez, A. (2007). Successful Topical Respiratory Tract Immunization of Primates against Ebola Virus. J. Virol. 81: 6379-6388 [Abstract] [Full Text]