3Reported cases of DHF by years in Thailand (1958-2004) Case (x10,000)Year
4Center for Vaccine Development, Mahidol University and WHO/TDR Reference Center on Dengue for Asia Table : Summary on dengue virus isolates from patients in Bangkok, Thailand,years
5Natural History There are four dengue virus serotypes, called DEN-1 DEN DEN-4They belong to the genus Flavivirus of Flaviviridaefamily.All 4 serotypes of Dengue infection are associatedwith Dengue hemorrhagic fever.
6OBJECTIVEThe overall objective of the programme is to develop a safe, effective and inexpensivelive attenuated tetravalent dengue vaccine.
7Parental Dengue Viruses Used for Attenuation Attempts
11Inoculation in 175 cm2 flask, using 5 ml inoculum Preparation of DEN-2 (16681) PDK 53 Vaccine, Production Lot. 1 in 20 x 175 cm2 flasks
12Live Attenuated Dengue Vaccine Biological Attributes 1. Plaque Size Morphology in LLC-MK2 Cells2. Cytopathic Effect in LLC-MK2 Cells3. Temperature Sensitivity4. Replication in Mononuclear Cells5. Suckling Mouse Neurovirulence6. Monkey Viremia and Antibody Response7. Infection, dissemination and transmission in mosquitoesStudy of Biological markers every 5 passages
13Comparison of plaque size morphology between DEN-4 parental strain and PDK passage 48 in LLC-MK2 cells
20Live Attenuated Tetravalent Dengue Vaccine Mahidol - Sanofi Pasteur,Monovalent and tetravalent vaccine trial (USA)Tetravalent vaccine trials in children 5-12 y.o. (Thailand)Cell substrate changed from PDK to Vero cellDEN-3 in Vero -Trials in Hong Kong-Highly reractogenicDEN-4 in Vero - high monkey viremiaDEN-1, DEN-2 in Vero - Trials in AustraliaComment : Still no DEN-3 and DEN-4 vaccine
21Current Dengue Vaccines at Advanced State of Development 1. Live attenuated tetravalent dengue PDK based vaccine1.1 MU/sp1.2 WRAIR-GSK* DEN-1, DEN-22. ChimeriVax (Yellow Fever Vaccine Platform)Acambis Inc. (USA + UK)* Monovalent DEN-2 - satisfactory (safety + immunogenicity)* Tetravalent vaccine - Seroconversion rate* Probably will require 3 doses* Booster effect?