Safety and immunogenicity of DNA vaccines encoding ebolavirus and marburgvirus wild-type glycoproteins in a phase i clinical trial

Uzma N. Sarwar, Pamela Costner, Mary E. Enama, Nina Berkowitz, Zonghui Hu, Cynthia S. Hendel, Sandra Sitar, Sarah Plummer, Sabue Mulangu, Robert T. Bailer, Richard A. Koup, John R. Mascola, Gary J. Nabel, Nancy J. Sullivan, Barney S. Graham, Julie E. Ledgerwood

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Background Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine. Methods The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay. Results The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzyme-linked immunosorbent assay results (30) at week 12. The fourth DNA vaccination boosted the immune responses. Conclusions The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens. Clinical Trials Registration NCT00605514.

Original languageEnglish (US)
Pages (from-to)549-557
Number of pages9
JournalJournal of Infectious Diseases
Volume211
Issue number4
DOIs
StatePublished - Feb 15 2015

Keywords

  • DNA
  • ebola
  • ebolavirus
  • filovirus
  • marburg
  • marburgvirus
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Safety and immunogenicity of DNA vaccines encoding ebolavirus and marburgvirus wild-type glycoproteins in a phase i clinical trial'. Together they form a unique fingerprint.

  • Cite this

    Sarwar, U. N., Costner, P., Enama, M. E., Berkowitz, N., Hu, Z., Hendel, C. S., Sitar, S., Plummer, S., Mulangu, S., Bailer, R. T., Koup, R. A., Mascola, J. R., Nabel, G. J., Sullivan, N. J., Graham, B. S., & Ledgerwood, J. E. (2015). Safety and immunogenicity of DNA vaccines encoding ebolavirus and marburgvirus wild-type glycoproteins in a phase i clinical trial. Journal of Infectious Diseases, 211(4), 549-557. https://doi.org/10.1093/infdis/jiu511