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

被引：119

作者：

Guy, Bruno ^{[1
]}

Nougarede, Nolwenn ^{[1
]}

Begue, Sarah ^{[1
]}

Sanchez, Violette ^{[1
]}

Souag, Nadia ^{[1
]}

Carre, Murielle ^{[1
]}

Chambonneau, Laurent ^{[1
]}

Morrisson, Dennis N. ^{[2
]}

Shaw, David ^{[3
]}

Qiao, Ming ^{[3
]}

Dumas, Rafaele ^{[1
]}

Lang, Jean ^{[1
]}

Forrat, Remi ^{[1
]}

机构：

[1] Sanofi Pasteur, Res Dept, Marcy Letoile, France

[2] Biokinet Clin Applicat, Springfield, MO USA

[3] Royal Adelaide Hosp, Adelaide, SA 5000, Australia

来源：

VACCINE | 2008年 / 26卷 / 45期

关键词：

Dengue vaccine; Human; Cellular immunity;

D O I：

10.1016/j.vaccine.2008.08.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5712 / 5721

页数：10

共 25 条

[1] Cross-reactive memory CD8+ T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner [J].