title: A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans.
abstract: A dengue-1 candidate vaccine (45AZ5), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for < or = 1 day in 4, and neutralizing antibody in all 10, which persisted for > or = 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: R
authors.initials: R
authors.lastname: Edelman
authors.forename: C O
authors.initials: CO
authors.lastname: Tacket
authors.forename: S S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: D W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: K H
authors.initials: KH
authors.lastname: Eckels
authors.forename: D R
authors.initials: DR
authors.lastname: Dubois
authors.forename: P L
authors.initials: PL
authors.lastname: Summers
authors.forename: C H
authors.initials: CH
authors.lastname: Hoke
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D002478:Cells, Cultured; D003715:Dengue / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D004285:Dogs; D005260:Female; D006801:Humans; D007668:Kidney; D008297:Male; D008875:Middle Aged; D012692:Serial Passage; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines