An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model.
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.
Robert Putnak
J
J
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
Coller
Beth-Ann
BA
Voss
Gerald
G
Vaughn
David W
DW
Clements
David
D
Peters
Iain
I
Bignami
Gary
G
Houng
Hou-Shu
HS
Chen
Robert C-M
RC
Barvir
David A
DA
Seriwatana
Jitvimol
J
Cayphas
Sylvie
S
Garçon
Nathalie
N
Gheysen
Dirk
D
Kanesa-Thasan
Niranjan
N
McDonell
Mike
M
Humphreys
Tom
T
Eckels
Kenneth H
KH
Prieels
Jean-Paul
JP
Innis
Bruce L
BL
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
D000914:Antibodies, Viral; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines