title: Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects.
abstract: Three independent, phase 1 clinical trials were conducted in Australia and in USA to assess the safety and immunogenicity of sanofi pasteur dengue vaccine candidates. In this context, Dengue 1-4 and Yellow Fever 17D-204 (YF 17D)-specific CD4 and CD8 cellular responses induced by tetravalent chimeric dengue vaccines (CYD) were analyzed in flavivirus-naive or flavivirus-immune patients. Tetravalent CYD vaccine did not trigger detectable changes in serum pro-inflammatory cytokines, whatever the vaccinees immune status, while inducing significant YF 17D NS3-specific CD8 responses and dengue serotype-specific T helper responses. These responses were dominated by serotype 4 in naive individuals, but a booster vaccination (dose #2) performed 4 months following dose #1 broadened serotype-specific responses. A similar, broader response was seen after primary tetravalent immunization in subjects with pre-existing dengue 1 or 2 immunity caused by prior monovalent live-attenuated dengue vaccination. In all three trials, the profile of induced response was similar, whatever the subjects' immune status, i.e. an absence of Th2 response, and an IFN-gamma/TNF-alpha ratio dominated by IFN-gamma, for both CD4 and CD8 responses. Our results also showed an absence of cross-reactivity between YF 17D or Dengue NS3-specific CD8 responses, and allowed the identification of 3 new CD8 epitopes in the YF 17D NS3 antigen. These data are consistent with the previously demonstrated excellent safety of these dengue vaccines in flavivirus-naive and primed individuals.
authors.affiliation: Research Department, sanofi pasteur, Marcy l'Etoile, France. bruno.guy@sanofipasteur.com
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Nougarede
authors.forename: Sarah
authors.initials: S
authors.lastname: Begue
authors.forename: Violette
authors.initials: V
authors.lastname: Sanchez
authors.forename: Nadia
authors.initials: N
authors.lastname: Souag
authors.forename: Murielle
authors.initials: M
authors.lastname: Carre
authors.forename: Laurent
authors.initials: L
authors.lastname: Chambonneau
authors.forename: Dennis N
authors.initials: DN
authors.lastname: Morrisson
authors.forename: David
authors.initials: D
authors.lastname: Shaw
authors.forename: Ming
authors.initials: M
authors.lastname: Qiao
authors.forename: Rafaele
authors.initials: R
authors.lastname: Dumas
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
authors.forename: Remi
authors.initials: R
authors.lastname: Forrat