title: Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region.
abstract: The recombinant dengue virus type-4 vaccine candidate 2AA30 was attenuated in rhesus monkeys due to an engineered 30-nucleotide deletion in the 3'-untranslated region of the viral genome. A clinical trial to evaluate the safety and immunogenicity of a single dose of 2Adelta30 was conducted with 20 adult human volunteers. The vaccine candidate was well tolerated and did not cause systemic illness in any of the 20 volunteers. Viremia was detectable in 14 volunteers at a mean level of 1.6 log10 plaque-forming units/ml of serum, although all 20 volunteers seroconverted with a seven-fold or greater increase in serum neutralizing antibody titer on day 28 post-vaccination (mean titer = 1:580). A mild, asymptomatic, macular rash developed in 10 volunteers, and a transient elevation in the serum level of alanine aminotransferase was noted in five volunteers. The low level of reactogenicity and high degree of immunogenicity of this vaccine candidate warrant its further evaluation and its use to create chimeric vaccine viruses expressing the structural genes of dengue virus types 1, 2, and 3.
authors.affiliation: Center for Immunization Research, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Durbin
authors.forename: R A
authors.initials: RA
authors.lastname: Karron
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: D W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: M J
authors.initials: MJ
authors.lastname: Reynolds
authors.forename: J R
authors.initials: JR
authors.lastname: Perreault
authors.forename: B
authors.initials: B
authors.lastname: Thumar
authors.forename: R
authors.initials: R
authors.lastname: Men
authors.forename: C J
authors.initials: CJ
authors.lastname: Lai
authors.forename: W R
authors.initials: WR
authors.lastname: Elkins
authors.forename: R M
authors.initials: RM
authors.lastname: Chanock
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
authors.forename: S S
authors.initials: SS
authors.lastname: Whitehead
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D000328:Adult; D000818:Animals; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007114:Immunization; D008253:Macaca mulatta; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines