Modification of dengue virus strains by passage in primary dog kidney cells: preparation of candidate vaccines and immunization of monkeys.
Dengue (DENV) virus strains for each of the four DENV serotypes were modified by passage in primary dog kidney (PDK) cell cultures with final manufacture of vaccine lots in fetal rhesus monkey diploid cell cultures. "Strain sets" consisting of serially-passaged DENV were inoculated in rhesus monkeys along with unmodified parent viruses for each strain. Vaccine candidates were compared with unmodified parent viruses by measuring viremia and immune responses. All except one DENV-1 strain demonstrated reduced infection in monkeys after PDK cell passage. A DENV-3 strain lost all monkey infectivity after PDK cell passage. Twelve vaccine candidates were selected for Phase 1 human trials through this selection process.
Eckels
Kenneth H
KH
Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
Dubois
Doria R
DR
Putnak
Robert
R
Vaughn
David W
DW
Innis
Bruce L
BL
Henchal
Erik A
EA
Hoke
Charles H
CH
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002478:Cells, Cultured; D017321:Clinical Trials, Phase I as Topic; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D004285:Dogs; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D012692:Serial Passage; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D014766:Viremia; D014776:Virus Cultivation
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines