Development of a Flexible, Live Tetravalent Dengue Vaccine

In this proposal, we will further the development of a tetravalent live-attenuated Dengue Virus (DENV) vaccine capable meeting the needs of the deploying warfighter, including durable/broad immunity against ALL four serotypes. The Armed Forces Medical Intelligence has ranked DENV as the third most significant natural infectious threat behind only malaria and bacterial diarrhea to our deploying troops. Currently the US military does not have an effective anti-DENV vaccine. Operational evidence shows that deploying US warfighters continue to contract and suffer from DENV. The development of an effective dengue vaccine is vital to prevent loss of mission readiness. In Phase II, we will utilize our Synthetic-biology based platform to construct human-cell deoptimized DENV vaccine strains – allowing us to balance all four serotypes in a single vaccine to ensure an immune response to all strains. Each of the four live-attenuated vaccine DENV strains will be constructed in its own homologous backbone to overcome limitations of other competitor DENV vaccine candidates. Phase II will conclude with a re-balanced tetravalent vaccine with demonstration of safety and efficacy in a Non-Human Primate Model that is ready GMP manufacturing and a Phase I/II clinical trial in Phase III work.