title: Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore.
abstract: To characterize the cell mediated immunity (CMI) induced by the investigational CYD tetravalent dengue vaccine (TDV), we developed a whole-blood, intracellular cytokine staining (ICS) assay and a multiplex assay, each requiring 3 mL of blood. We assessed CMI before and 28 d after a first and third injection of CYD-TDV and one year after the third injection in a subset of 80 adolescents and adults enrolled in a phase II trial in Singapore (ClinicalTrial.gov NCT NCT00880893). CD4/IFNγ/TNFα responses specific to dengue NS3 were detected before vaccination. Vaccination induced YF-17D-NS3-specific CD8/IFNγ responses, without significant TNFα, and a CYD-specific Th1/Tc1 cellular response in all participants, which was characterized by predominant IFNγ secretion compared with TNFα, associated with low level IL-13 secretion in multiplex analysis of peripheral blood mononuclear cells (PBMC) supernatants after restimulation with each the CYD vaccine viruses. Responses were directed mainly against CYD-4 after the first vaccination, and were more balanced against all four serotypes after the third vaccination. The same qualitative profile was observed one year after the third vaccination, with approximately 2-fold lower NS3-specific responses, and 3-fold lower serotype-specific cellular responses. These findings confirm previous observations regarding both the nature and specificity of cellular responses induced by CYD-TDV, and for the first time demonstrate the persistence of cellular responses after one year. We also established the feasibility of analyzing CMI with small blood samples, allowing such analysis to be considered for pediatric trials.
authors.affiliation: Research & Development; Sanofi pasteur; Marcy l'Etoile, France.
authors.forename: Anke
authors.initials: A
authors.lastname: Harenberg
authors.forename: Sarah
authors.initials: S
authors.lastname: Begue
authors.forename: Audrey
authors.initials: A
authors.lastname: Mamessier
authors.forename: Sophie
authors.initials: S
authors.lastname: Gimenez-Fourage
authors.forename: Ching
authors.initials: C
authors.lastname: Ching Seah
authors.forename: Ai
authors.initials: A
authors.lastname: Wei Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Li Ng
authors.forename: Xue
authors.initials: X
authors.lastname: Yun Toh
authors.forename: Sophia
authors.initials: S
authors.lastname: Archuleta
authors.forename: Annelies
authors.initials: A
authors.lastname: Wilder-Smith
authors.forename: Lynette P
authors.initials: LP
authors.lastname: Shek
authors.forename: Anh
authors.initials: A
authors.lastname: Wartel-Tram
authors.forename: Alain
authors.initials: A
authors.lastname: Bouckenooghe
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
authors.forename: Denis
authors.initials: D
authors.lastname: Crevat
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillet
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012846:Singapore; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D016207:Cytokines; D053059:Dengue Vaccines
keywords: cell mediated immunity; cytokines; intracellular cytokine staining; tetravalent dengue vaccine; whole blood