Use of the Dual Platform Immunization (DuPI) Approach to Develop a Tetravalent Dengue Vaccine

Dengue, the most important mosquito born virus infection worldwide, is a public health threat in many tropical and subtropical areas of the world. Military personnel conducting operations in these areas are at high risk for getting dengue, which can make a person sick for days to weeks rendering them unable to perform their duties. The best way to prevent a person from getting dengue is to develop a protective vaccine. Using mosquito bed nets and repellents has not proven to be effective in the military population in preventing dengue in operational settings. We have developed a unique way to produce a killed virus vaccine using a compound called psoralen, together with UV light. This method of killing dengue virus leaves the outside protein coat of the virus intact, which can be recognized much better by the immune system to produce a response that will protect an individual from becoming naturally infected with dengue. We have also done some preliminary work looking at combining two different types of vaccines (made using different methods or platforms) and administering them together in a single injection. Using this dual platform immunization (DuPI) method, combining the psoralen killed vaccine with a dengue DNA vaccine, we demonstrated an immune response in mice that was better than the immune response using either vaccine alone. The goal of this proposal is to further pursue developing a dengue vaccine using the DuPI method involving these two vaccines. Also, we will further explore the use of the psoralen killed vaccine as a standalone vaccine if in additional animal studies it proves to be as good as or better than the DuPI approach.