Dengue virus is endemic throughout the tropical regions of the world. Vaccination against dengue virus is the most promising tool to control dengue infection, as there is currently no dengue specific antiviral treatment. While the licensure of Dengvaxia was a significant step forward for dengue vaccine development, due to the limitations surrounding its efficacy and implementation in dengue-endemic countries, alternative vaccines have remained a priority.
The development of a new chimeric insect-specific flavivirus system, has allowed the production of multiple flaviviral vaccine candidates. By exchanging the structural prM and E proteins of BinJV with those of pathogenic vertebrate-infecting flaviviruses (VIFs), a chimeric virus (bVIF) was generated that is antigenically indistinguishable from the pathogenic parental virus. The safety profile of these chimeras and their authentic presentation quaternary epitopes are essential for eliciting neutralising antibodies, making these viruses potential alternative vaccine candidates. To further enhance the immune response, we used an alternative vaccine delivery system, the High-Density Microarray Patch (HD-MAP), which has been designed to target vaccine antigens to the skin layers rich in antigen presenting cells.
This study describes the stability of the chimeric viruses dried on the HD-MAP and evaluates four chimeric dengue virus vaccines (bDENV) as either a monovalent or tetravalent vaccine formulation delivered by HD-MAP and intramuscular injection. These chimeric viruses elicited potent neutralising antibodies against both homologous and heterologous serotypes. Neutralising antibodies induced by both the monovalent and tetravalent vaccine formulation were raised to equal levels with no immunodominance observed for any serotype. In addition, when coupled with the HD-MAP, enhanced antibody kinetics is observed, resulting in higher levels of neutralising antibodies elicited just after a single dose. These chimeric viruses, coupled with skin targeted delivery, offer a promising new vaccine platform as well as an attractive alternative in mass vaccination settings.