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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.

Authors’ addresses: Kenneth H. Eckels, Robert Putnak, David W. Vaughn, Medical Infections Diseases Research Program, U.S. Army Medical Research and Material Command, Ft. Detrick, Frederick, MD 21702-5012, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910. Doria R. Dubois, Vaccine Research Center, Building 40, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892. Bruce L. Innis, GlaxoSmithKline, 1250 South Collegeville Road, Mail Code UP4330, Collegeville, PA 19426-0989. Erik A. Henchal, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick MD 21702-5011. Charles H. Hoke, Anteon Corp., Medical Systems Program, U.S. Army Medical Research and Material Command, Ft. Detrick, Frederick, MD 21702-5012.

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