Novel Adjuvants to Enhance the Immunogenicity of a Dengue Vaccine

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a tremendous public health threat throughout the world. The U.S. military has also been challenged by dengue for over a hundred years and the pursuit of an effective DENV vaccine is a high priority for the Department of Defense (DoD). Despite over 70 years of efforts, there is still no registered dengue vaccine. While significant progress has been made in the last decade, challenges still remain. To help enhance development of a DENV vaccine candidate there two key areas that need to be addressed; robust immunogenicity, both antibody titers and durability, and shorting the duration of immunization schedule. This application is directed at demonstrating the enhanced immunogenicity of formulations comprised of an inactivated DENV and novel adjuvants. The use of novel adjuvants with the potential for clinical use will help accelerate the development of an enhanced inactivated DENV vaccine. For the first phase of this effort the technical objectives are to first screen and select formulations with robust immunogenicity and then to demonstrate protective efficacy in a lethal mouse challenge model. In this manner we will demonstrate the feasibility of developing an adjuvanted-inactivated dengue vaccine with enhanced and durable immune responses.