Abstract
An estimated 400 million people in the world are infected with any of the four types of dengue virus (DENV) annually. The only licensed dengue vaccine cannot effectively prevent infection with all of the four DENVs, especially in those immunologically naïve at baseline. In this study, we explored a mosaic vaccine approach, which utilizes an artificial recombinant sequence for each serotype to achieve maximum coverage of variant epitopes in the four DENVs. We determined the immunogenicity and cross-reactivity of DNA plasmids encoding individual mosaic sequences or the natural sequences in mice. We show that the mosaic vaccines, particularly those targeting DENV serotype 1 and 2, improved vaccine immunogenicity by increasing the percentage of antigen-specific IFNγ- or TNFα-secreting CD4 and CD8 T cells, and titers of neutralizing antibodies. The mosaic vaccine diversified and broadened anti-dengue T cell responses and cross-reactive neutralizing antibodies against all four serotypes. The mosaic vaccines also induced higher level of antigen-specific B cell responses. These results suggest that mosaic vaccines comprising of DENV serotype 1 and 2 variant epitopes could stimulate strong and broad immune responses against all four serotypes.
Highlights
Dengue is a mosquito-borne viral disease caused by dengue viruses (DENV)
Our results indicate that the mosaic DENV1 and DENV2 DNA vaccine approach improves both the homotypic and heterotypic cellular and humoral immune responses to all four DENV serotypes
By comparing the mosaic precursor membrane (prM) and Env sequences to their respective wild type sequences, the mosaic sequences had a higher coverage of T cell epitopes than wild type sequences at most of the positions (Figures 1A,B)
Summary
Dengue is a mosquito-borne viral disease caused by dengue viruses (DENV). DENVs are a single stranded, positive sense RNA virus belonging to the flavivirus genus of the flaviviridae family [1, 2]. Subsequent infections with a different DENV may instead result in Dengue Mosaic Vaccines Are Immunogenic increased risk of severe dengue, which is characterized by hypovolemic shock from vascular leak, internal hemorrhage or organ dysfunction This increased risk of severe disease during secondary DENV infection could be contributed, at least in part, by antibody-dependent enhancement (ADE) [11], by which cross-reactive non- or sub-neutralizing levels of antibodies induced from the first infection bind heterotypic DENV to enable virus entry into target cells via Fc-gamma receptors (FcγR) [12,13,14]. A dengue vaccine that can prevent infection with all four DENVs remain a public health need
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
