Abstract
Dengue fever has become a global threat, causing millions of infections every year. An effective vaccine against all four serotypes of dengue virus (DENV) has not been developed yet. Among the different vaccination strategies available today, DNA vaccines are safe and practical, but currently induce relatively weak immune responses in humans. In order to improve immunogenicity, antigens may be targeted to dendritic cells (DCs), the main antigen presenting cells and orchestrators of the adaptive immune response, inducing T and B cell activation. It was previously shown that a DNA vaccine encoding a fusion protein comprised of an antigen and a single-chain Fv antibody (scFv) specific for the DC endocytic receptor DEC205 induced strong immune responses to the targeted antigen. In this work, we evaluate this strategy to improve the immunogenicity of dengue virus (DENV) proteins. Plasmids encoding the scFv αDEC205, or an isotype control (scFv ISO), fused to the DENV2 envelope protein domain III (EDIII) were generated, and EDIII specific immune responses were evaluated in immunized mice. BALB/c mice were intramuscularly (i.m.) immunized three times with plasmid DNAs encoding either scDEC-EDIII or scISO-EDIII followed by electroporation. Analyses of the antibody responses indicated that EDIII fusion with scFv targeting the DEC205 receptor significantly enhanced serum anti-EDIII IgG titers that inhibited DENV2 infection. Similarly, mice immunized with the scDEC-EDIII plasmid developed a robust CD4+ T cell response to the targeted antigen, allowing the identification of two linear epitopes recognized by the BALB/c haplotype. Taken together, these results indicate that targeting DENV2 EDIII protein to DCs using a DNA vaccine encoding the scFv αDEC205 improves both antibody and CD4+ T cell responses. This strategy opens perspectives for the use of DNA vaccines that encode antigens targeted to DCs as a strategy to increase immunogenicity.
Highlights
Dengue virus (DENV) is the causative agent of dengue fever, an infection that has become a serious public health issue
To demonstrate that scDEC-envelope protein domain III (EDIII) retained the capacity to bind to the DEC205 receptor, CHO cells stably expressing the murine DEC205 receptor were incubated with different concentrations of either scDEC-EDIII or scISOEDIII
These results indicate that both single-chain Fv antibody (scFv) were successfully secreted from transiently transfected cells, and that the scDEC-EDIII preserved its binding capacity to the DEC205 receptor
Summary
Dengue virus (DENV) is the causative agent of dengue fever, an infection that has become a serious public health issue. The E protein plays an important role in the protective immunity against DENV as it contains the majority of epitopes that elicit neutralizing antibodies [4,5,6]. This protein can be divided into three domains: the central domain (EDI), the domain responsible for dimerization containing the fusion peptide (EDII), and the domain that binds to the surface cell receptor (EDIII) [2]. In addition to neutralizing antibodies, T cell responses play a relevant role in the development of protection. IFNγ-secreting Th1 and CX3CR1+ cytotoxic CD4+ T cells are associated with protection [12, 13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
