title: Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naïve adults.
abstract: Sixteen dose formulations of our live-attenuated tetravalent dengue virus vaccines (TDV) were previously evaluated for safety and immunogenicity. Two of the sixteen candidate TDV formulations (Formulations 13 and 14) were selected for further evaluation. A new TDV formulation, Formulation 17, using a higher primary dog kidney (PDK) cell passage Dengue-1 virus (DENV-1) and a lower PDK cell passage DENV-4, was developed to optimize the neutralizing antibody response. All three formulations consist of combinations of 10exp3-5 pfu/dose of the four dengue vaccine virus serotypes. This double-blind, randomized trial in 71 healthy adult subjects evaluated vaccine safety, reactogenicity and immunogenicity. TDV's were given subcutaneously in the deltoid on Day 0 and 180 (6 months). Subjects were seen in clinic on Study Days 0, 10, 28, 180, 190 and 208 and filled out daily symptom diaries for 21 days after each vaccination. Formulation 13 was the most reactogenic, while both Formulations 14 and 17 were similar in reported reactions. Seventy-five percent, 31% and 31% of subjects were viremic on Day 10 after primary vaccination with Formulations 13, 14 and 17 respectively. Viremia was not detected in any subject following the second dose of vaccine. The immunogenicity endpoint was neutralizing antibody titer one month after the second vaccination. Thirty-six percent, 40% and 63% of vaccinated subjects developed tetravalent neutralizing antibodies after two doses of Formulations 13, 14 and 17, respectively. Formulation 17 was selected for further clinical evaluation based on this study.
authors.affiliation: Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Wellington
authors.initials: W
authors.lastname: Sun
authors.forename: Dennis
authors.initials: D
authors.lastname: Cunningham
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: Judith
authors.initials: J
authors.lastname: Perry
authors.forename: J Robert
authors.initials: JR
authors.lastname: Putnak
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Eckels
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kanesa-Thasan
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.forename: Robert
authors.initials: R
authors.lastname: Edelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014766:Viremia; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated