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

• Published in: Vaccine 2008-10, Vol.26 (45), p.5712-5721
• Main Authors: Guy, Bruno, Nougarede, Nolwenn, Begue, Sarah, Sanchez, Violette, Souag, Nadia, Carre, Murielle, Chambonneau, Laurent, Morrisson, Dennis N, Shaw, David, Qiao, Ming, Dumas, Rafaele, Lang, Jean, Forrat, Remi
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Arboviroses; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cellular immunity; Clinical trials; Cytokines - metabolism; Dengue - immunology; Dengue - prevention & control; Dengue - virology; Dengue fever; Dengue fevers; Dengue vaccine; Dengue Vaccines - administration & dosage; Dengue Vaccines - adverse effects; Dengue Vaccines - immunology; Dengue Virus - immunology; Fundamental and applied biological sciences. Psychology; Human; Human viral diseases; Humans; Immune status; Immune system; Immunization; Immunogenicity; Infections; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Peptides; Th1 Cells - immunology; Th2 Cells - immunology; Treatment Outcome; Tropical viral diseases; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vector-borne diseases; Viral diseases; Virology; Yellow Fever - immunology; Yellow Fever - prevention & control; Yellow Fever - virology; Yellow fever virus - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.08.019

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-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.