title: An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model.
abstract: The safety, immunogenicity, and protective efficacy of two non-replicating antigen-based vaccines and one live-attenuated virus (LAV) vaccine for dengue type-2 (dengue-2) virus were evaluated in the rhesus macaque model. The non-replicating vaccines consisted of whole, purified inactivated virus (PIV) and a recombinant subunit protein containing the amino-(N)-terminal 80% of envelope protein (r80E), each formulated with one of five different adjuvants. Each formulation was administered to three animals on a 0, 3-month schedule. Following the primary immunizations, 37 of 39 animals demonstrated dengue-2 virus neutralizing antibodies. After the booster immunizations all animals had dengue neutralizing antibodies with peak titers ranging from 1:100 to 1:9700. The highest neutralizing antibody titers were observed in the groups that received r80E antigen formulated with AS04, AS05, or AS08 adjuvant, and PIV formulated with AS05 or AS08 adjuvant. These newer adjuvants are based on alum, fraction QS-21 of saponin, and monophosphoryl lipid A (MPL). Protection was evaluated by dengue-2 virus challenge 2 months after the booster by the measurement of circulating virus (viremia) and post-challenge immune responses. Several groups exhibited nearly complete protection against viremia by bioassay, although there was evidence for challenge virus replication by Taqmantrade mark and immunological assays. None of the vaccines conferred sterile immunity.
authors: Walter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. robert.putnak@na.amedd.army.mil
authors: J
authors: J
authors: Robert Putnak
authors: Beth-Ann
authors: BA
authors: Coller
authors: Gerald
authors: G
authors: Voss
authors: David W
authors: DW
authors: Vaughn
authors: David
authors: D
authors: Clements
authors: Iain
authors: I
authors: Peters
authors: Gary
authors: G
authors: Bignami
authors: Hou-Shu
authors: HS
authors: Houng
authors: Robert C-M
authors: RC
authors: Chen
authors: David A
authors: DA
authors: Barvir
authors: Jitvimol
authors: J
authors: Seriwatana
authors: Sylvie
authors: S
authors: Cayphas
authors: Nathalie
authors: N
authors: Garçon
authors: Dirk
authors: D
authors: Gheysen
authors: Niranjan
authors: N
authors: Kanesa-Thasan
authors: Mike
authors: M
authors: McDonell
authors: Tom
authors: T
authors: Humphreys
authors: Kenneth H
authors: KH
authors: Eckels
authors: Jean-Paul
authors: JP
authors: Prieels
authors: Bruce L
authors: BL
authors: Innis
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D004334:Drug Administration Schedule; D007114:Immunization; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000145:classification / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000914:Antibodies, Viral; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines