title: Efficacy of a live attenuated tetravalent candidate dengue vaccine in naïve and previously infected cynomolgus macaques.
abstract: The development of a safe and effective vaccine against dengue is a public health priority. Attempts to evaluate candidate vaccine formulations in human volunteers were largely unsuccessful, at least in part due to too high reactogenicity of some of the candidate vaccines tested. We evaluated a live attenuated tetravalent dengue vaccine candidate in flavivirus naïve and dengue virus type 3 immune non-human primates. Immune responses were measured both at the humoral and the cellular level and the efficacy of this vaccine candidate was evaluated by challenging the vaccinated animals with dengue virus type 4. Humoral and cellular immune responses upon vaccination were similar to those described after natural infection in humans. All animals were protected from developing viremia upon challenge infection. In addition, primary dengue virus type 3 infection of macaques neither influenced the immune response upon vaccination, nor interfered with vaccine-induced protection from dengue virus type 4 challenge infection. The data suggest that the live attenuated tetravalent vaccine candidate used is promising and warrant further safety and efficacy testing in clinical trials.
authors.affiliation: Department of Virology, Erasmus MC, Dr. Molewaterplein 50, 3015GE Rotterdam, The Netherlands.
authors.forename: Penelopie
authors.initials: P
authors.lastname: Koraka
authors.forename: Sabrina
authors.initials: S
authors.lastname: Benton
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Koert J
authors.initials: KJ
authors.lastname: Stittelaar
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014709:Vero Cells; D014766:Viremia / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012367:RNA, Viral; D007371:Interferon-gamma