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 (PI...

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Bibliographic Details
Published in:Vaccine 2005-08, Vol.23 (35), p.4442-4452
Main Authors: Robert Putnak, J., Coller, Beth-Ann, Voss, Gerald, Vaughn, David W., Clements, David, Peters, Iain, Bignami, Gary, Houng, Hou-Shu, Chen, Robert C.-M., Barvir, David A., Seriwatana, Jitvimol, Cayphas, Sylvie, Garçon, Nathalie, Gheysen, Dirk, Kanesa-thasan, Niranjan, McDonell, Mike, Humphreys, Tom, Eckels, Kenneth H., Prieels, Jean-Paul, Innis, Bruce L.
Format: Article
Language:English
Subjects:
Adjuvants
Animals
Antibodies, Viral - blood
Antigens
Applied microbiology
Biological and medical sciences
Candidates
Dengue - prevention & control
Dengue fever
Dengue type-2 virus
Dengue Virus - classification
Dengue Virus - genetics
Dengue Virus - immunology
Dengue virus type 2
Drug Administration Schedule
Fundamental and applied biological sciences. Psychology
Gene expression
Immunization
Infections
Live-attenuated
Macaca mulatta
Microbiology
Miscellaneous
Non-replicating antigen-based
Proteins
Recombinant Proteins - administration & dosage
Recombinant Proteins - immunology
Vaccine
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Attenuated - administration & dosage
Vaccines, Attenuated - adverse effects
Vaccines, Attenuated - immunology
Viral Vaccines - administration & dosage
Viral Vaccines - classification
Viral Vaccines - immunology
Virology
Virus Replication - drug effects
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Summary: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 Taqman™ and immunological assays. None of the vaccines conferred sterile immunity.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2005.03.042