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Research Paper
Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naïve adults
Wellington Sun, Dennis Cunningham, Steven S. Wasserman, Judith Perry, J. Robert Putnak, Kenneth H. Eckels, David W. Vaughn, Stephen J. Thomas , Niranjan Kanesa-Thasan, Bruce L. Innis and Robert Edelman
volume 4 | issue 6
november/december 2008Subscribe to this journal for $79/year
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
Wellington Sun
Department of Virus Diseases; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
Dennis Cunningham
Department of Medicine and the Center for Vaccine Development; University of Maryland School of Medicine; Baltimore, Maryland USA
Steven S. Wasserman
Department of Medicine and the Center for Vaccine Development; University of Maryland School of Medicine; Baltimore, Maryland USA
Judith Perry
University Health Center; University of Maryland; College Park, Maryland USA
J. Robert Putnak
Department of Virus Diseases; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
Kenneth H. Eckels
Department of Biologics Research; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
David W. Vaughn
Department of Virus Diseases; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
Stephen J. Thomas
Department of Virus Diseases; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
Niranjan Kanesa-Thasan
Department of Virus Diseases; Walter Reed Army Institute of Research; Silver Spring, Maryland USA
Bruce L. Innis
GlaxoSmithKline Biologicals; King of Prussia, Pennsylvania USA
Robert Edelman
Department of Medicine and the Center for Vaccine Development; University of Maryland School of Medicine; Baltimore, Maryland USA