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Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects

2008; Elsevier BV; Volume: 26; Issue: 45 Linguagem: Inglês

10.1016/j.vaccine.2008.08.019

1873-2518

Bruno Guy, Nolwenn Nougarede, Sarah Begue, Violette Sanchez, Nadia Souag, Murielle Carre, Laurent Chambonneau, Dennis N. Morrisson, David Shaw, Ming Qiao, Rafaele Dumas, Jean Lang, Rémi Forrat,

Viral Infections and Vectors

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-γ/TNF-α ratio dominated by IFN-γ, 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.