title: Protection of Rhesus monkeys against dengue virus challenge after tetravalent live attenuated dengue virus vaccination.
abstract: Rhesus monkeys develop viremia after dengue virus (DENV) inoculation and have been used as an animal model to study DENV infection and DENV vaccine candidates. We evaluated, in this model, the protective efficacy of a live attenuated tetravalent DENV vaccine (TDV) candidate against parenteral challenge with parental near-wild-type DENV strains. Twenty monkeys were vaccinated with TDV at 0 and 1 month, and 20 unvaccinated monkeys served as controls. Vaccinated animals and their controls were inoculated with 10(3)-10(4) pfu of challenge virus 4.5 months after the second vaccination. Primary vaccination resulted in 95%, 100%, 70%, and 15% seroconversion to DENV serotypes 1, 2, 3, and 4 (DENV-1, -2, -3, and -4), respectively. After the second vaccination, the seropositivity rates were 100%, 100%, 90%, and 70%, respectively. Vaccination with TDV resulted in complete protection against viremia from DENV-2 challenge and in 80%, 80%, and 50% protection against challenge with DENV-1, -3, and -4, respectively. Our results suggest that the TDV can elicit protective immunity against all 4 DENV serotypes. Interference among the 4 vaccine viruses may have resulted in decreased antibody responses to DENV-3 and -4, which would require reformulation or dose optimization to minimize this interference during testing of the vaccine in humans.
authors.affiliation: Department of Virus Diseases, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. wellinton.sun@us.army.mil
authors.forename: Wellington
authors.initials: W
authors.lastname: Sun
authors.forename: Ananda
authors.initials: A
authors.lastname: Nisalak
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Eckels
authors.forename: J Robert
authors.initials: JR
authors.lastname: Putnak
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Endy
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D007117:Immunization, Secondary; D008253:Macaca mulatta; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines