Boost-Phase Sub-Unit Vaccine Development for Binary Vaccines Against Infectious Diseases and Biological Warfare Agents

Malaria is a serious threat to people including military personal in endemic areas. So far no prophylactic vaccine is available. The aim of this study is to develop a powerful prime/boost vaccination protocol against malaria using DNA vaccines to primethe immune system and recombinant adenovirus vectors to boost it. The hypothesis is that topical application of adenovirus vectors will strengthen the cellular and humoral immune responses induced by DNA vaccines. The intranasal inoculation ofadenovirus is supposed to specifically boost the humoral immune response primed by DNA vaccines. Adenovirus vectors have a good safety record. Adenovirus itself is ubiquitous without causing serious health problems. Adenovirus has also been used inextensive vaccination programs without problems. The vectors are replication incompetent and the amount of vector introduced is far below the toxic level. In these studies, we will evaluate prime/boost protocols using adenovirus vectors to develop aprophylactic vaccine against malaria. We will also compare the protocols developed in this proposal to their counterparts using intramuscular injected DNA vaccines. The line of investigation proposed herein may allow the development of efficacious andsafe vaccination protocols against malaria infection and may serve as a useful platform technology for other infectious diseases. The DNA-based prime/boost vaccine as proposed in these studies could arrive as the first prophylactic vaccine against malariainfection if its efficacy and safety should appear superior to other methods. People living in endemic areas, military personal deployed to the tropics and subtropics and travelers would greatly benefit from an effective malaria vaccine. The platformtechnology may be used against other infectious diseases as well.