title: A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for hemorrhagic fever with renal syndrome.
abstract: Candidate DNA vaccines for hemorrhagic fever with renal syndrome expressing the envelope glycoprotein genes of Hantaan (HTNV) or Puumala (PUUV) viruses were evaluated in an open-label, single-center Phase 1 study consisting of three vaccination groups of nine volunteers. The volunteers were vaccinated by particle-mediated epidermal delivery (PMED) three times at four-week intervals with the HTNV DNA vaccine, the PUUV DNA vaccine or both vaccines. At each dosing, the volunteers received 8 μg DNA/4 mg gold. There were no study-related serious adverse events, and all injection site pain was graded as mild. The most commonly reported systemic adverse events were fatigue, headache, malaise, myalgia, and lymphadenopathy. Blood samples were collected on days 0, 28, 56, 84, 140, and 180, and assayed for the presence of neutralizing antibodies. In the single vaccine groups, neutralizing antibodies to HTNV or PUUV were detected in 30% or 44% of individuals, respectively. In the combined vaccine group, 56% of the volunteers developed neutralizing antibodies to one or both viruses. These results demonstrate that the HTNV and PUUV DNA vaccines are safe and can be immunogenic in humans when delivered by PMED.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, United States.
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Boudreau
authors.forename: Matthew
authors.initials: M
authors.lastname: Josleyn
authors.forename: Diane
authors.initials: D
authors.lastname: Ullman
authors.forename: Diana
authors.initials: D
authors.lastname: Fisher
authors.forename: Lonnie
authors.initials: L
authors.lastname: Dalrymple
authors.forename: Karen
authors.initials: K
authors.lastname: Sellers-Myers
authors.forename: Peter
authors.initials: P
authors.lastname: Loudon
authors.forename: Janice
authors.initials: J
authors.lastname: Rusnak
authors.forename: Robert
authors.initials: R
authors.lastname: Rivard
authors.forename: Connie
authors.initials: C
authors.lastname: Schmaljohn
authors.forename: Jay W
authors.initials: JW
authors.lastname: Hooper
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D019470:Biolistics; D005260:Female; D018063:Hantaan virus / Q000276:immunology / Q000472:pathogenicity*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D029262:Puumala virus / Q000276:immunology / Q000472:pathogenicity*; 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: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines