Dengue-4 vaccine: neurovirulence, viraemia and immune responses in rhesus and cynomolgus monkeys.
A dengue 4 (DEN-4, strain 1036-PDK 48) vaccine attenuated by passage in primary dog kidney cells was tested using rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) monkeys to determine its safety, potency, and immunogenicity. 14 rhesus monkeys were divided into 3 groups: group 1, 2 animals given control culture fluid; group 2, 2 animals given DEN-4 parental virus; group 3, 10 animals given DEN-4 vaccine virus. 10 cynomolgus were similarly grouped, but group 3 contained 6 monkeys. No significant neurovirulence was observed with parental or with DEN-4 virus passaged in primary dog kidney (PDK) cells. Both cynomolgus monkeys inoculated with DEN-4 vaccine virus developed minimal (V-1) and mild (V-2) neurovirulence-type lesions in the central nervous system, which were nondestructive in both species. All parental and vaccine viruses produced moderate to high neutralizing antibody titres. Only parental virus produced viraemia, in 2 cynomolgus monkeys. Because of its safety and avirulence in monkeys, PDK 48 is recommended for human trial.
Angsubhakorn
S
S
Department of Pathobiology, Faculty of Science, and Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Yoksan
S
S
Bhamarapravati
N
N
Moe
J B
JB
Marchette
N J
NJ
Pradermwong
A
A
Sahaphong
S
S
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001927:Brain Diseases / Q000209:etiology; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009500:Neutralization Tests; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia; D014774:Virulence
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines