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.