title: Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial.
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.
  
  
  BACKGROUND
  NCT00605514.
authors.affiliation: Vaccine Research Center.
authors.forename: Uzma N
authors.initials: UN
authors.lastname: Sarwar
authors.affiliation: Vaccine Research Center.
authors.forename: Pamela
authors.initials: P
authors.lastname: Costner
authors.affiliation: Vaccine Research Center.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.affiliation: Vaccine Research Center.
authors.forename: Nina
authors.initials: N
authors.lastname: Berkowitz
authors.affiliation: Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Vaccine Research Center.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Hendel
authors.affiliation: Vaccine Research Center.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sitar
authors.affiliation: Vaccine Research Center.
authors.forename: Sarah
authors.initials: S
authors.lastname: Plummer
authors.affiliation: Vaccine Research Center.
authors.forename: Sabue
authors.initials: S
authors.lastname: Mulangu
authors.affiliation: Vaccine Research Center.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Vaccine Research Center.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Vaccine Research Center.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.affiliation: Vaccine Research Center.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Sullivan
authors.affiliation: Vaccine Research Center.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: Vaccine Research Center.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D008297:Male; D029024:Marburgvirus / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D046129:Ebola Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: DNA; ebola; ebolavirus; filovirus; marburg; marburgvirus; vaccine