THE TETRAVALENT LIVE ATTENUATED VIRUS APPROACH TO DENGUE VACCINE DEVELOPMENT
THE TETRAVALENT LIVE-ATTENUATED VIRUS APPROACH TO DENGUE VACCINE DEVELOPMENT: A HISTORICAL ACCOUNT LEADING TO PRESENT-DAY PEDIATRIC TRIALS Mammen P. Mammen, Jr.1, Charity Ann Ypil-Butac1, Veerachai Watanaveeradej2, Sriluck Simasathien2, Bruce L. Innis3, Ananda Nisalak1, Timothy P. Endy4, Stephen Thomas4, Kenneth H. Eckels4, Robert Putnak4, Robert V. Gibbons1, Wellington Sun4 1Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand 2Phramongkutklao Hospital, Bangkok, Thailand 3GlaxoSmithKline (GSK) Pennsylvania, USA 4Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA Background: Non-human primates have served as a model to guide dengue vaccine development. Historical non-human primate studies form the basis of the live-attenuated virus approach in which monovalent viruses of each serotype are combined into a tetravalent vaccine formulation. The WRAIR, in collaboration with GSK, has utilized this approach in recent pediatric trials. Objective: To provide a historical chronology of development of a live-attenuated dengue vaccine. Significance: Personal protective and vector control measures are considered impractical to protect populations against dengue. Study Design: Descriptive account of historical non-human primate studies followed by a randomized, double-blinded, controlled infant dengue vaccine study. Study Population: 51 flavivirus-naïve infants in Bangkok 12-15 months of age Methods: Infants were randomly assigned to receive either dengue vaccine at study months 0 and 6 (N=34) or control vaccines (varicella at study month 0; Hemophilus influenza B at study month 6) (N=17). Results: All infants tolerated the vaccinations without serious adverse events attributed to vaccination. Conclusion: The live-attenuated dengue vaccine approach appears to show promise till present-day pediatric trials. |
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