Journal
VACCINE
Volume 35, Issue 46, Pages 6308-6320Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2017.09.063
Keywords
Consensus envelope sequence; Tetravalent dengue vaccine; Balanced immunogenicity; Antibody response; Antibody dependent enhancement; T cell response
Categories
Funding
- Chinese Ministry of Science and Technology [2016YFC1201000]
- National Science Foundation of China [31670941, 31300757]
- Chinese Academy of Sciences (STS) [KFJEWSTS098]
- Chinese Academy of Sciences (Pilot Pioneer B Program) [XDPB0.0405]
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Dengue viruses (DENVs) are re-emerging pathogens transmitted by mosquitoes mainly in tropical and subtropical regions. Each year, they are estimated to infect 390 million people globally. The major challenge confronting dengue vaccine development is the need to induce balanced, long lasting tetravalent immune responses against four co-circulating virus serotypes (DENV-I,-III,-IV), because primary infection by any one of which may predispose infected individuals to more severe diseases during a heterotypic secondary infection. Another difficulty is to select representative strains in vaccine design to provide cross-protection against most circulating virus strains. In this study, aimed at developing a tetravalent subunit vaccine with a representative single protein, we designed two vaccines (named cE80(D4) and cE80(max)) based on the consensus sequences of the ectodomain of envelope protein of 3127 DENV strains, and then expressed them in the baculovirus expression system. Both vaccines were capable of eliciting specific antibodies against all four DENV serotypes, and the predominant IgG subtype elicited by the two vaccines was IgG1. Moreover, these vaccines activated both type I and type II antigen-specific helper T cells that secreted IFN-gamma and 1L-4, respectively. This proof-of-concept study has set foundation for further optimization of a single protein-based tetravalent DENV vaccine. (C) 2017 Elsevier Ltd. All rights reserved.
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