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-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.
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Podrobná bibliografie
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Publikováno v
- Vaccine
Ročník 26; číslo 45; s. 5712 - 5721
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Hlavní autoři
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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
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Typ dokumentu
- Journal Article
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Jazyk
- English
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Vydáno
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Oxford
Elsevier Ltd
23. 10. 2008
Elsevier
Elsevier Limited
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Témata
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Bibliografie
- ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
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ISSN
- 0264-410X
1873-2518
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DOI
- 10.1016/j.vaccine.2008.08.019
