This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Funding source: CDC 200-2005-13891WNV, which was discovered in Africa in the late 1930s, was never considered to be as important a public health problem as the viruses mentioned above until it arrived in the flavivirus naive population of North America in 1999. Since that time, WNV has been responsible for thousands of cases of encephalitis, and hundreds of deaths. West Nile Virus is a single stranded, positive-sense RNA virus belonging to the family F1aviviridae. The virus is maintained in nature between mosquitoes and birds with humans, horses, domestic and wild animals serving as incidental hosts. Overall, approximately 80% of people that are infected are asymptomatic. Twenty percent develop mild symptoms including fever, headache, and body aches, nausea, vomiting, and sometimes swollen lymph glands or a skin rash on the chest, stomach and back. Less than 1 % infected with the virus will develop high fever, headache, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, vision Joss, numbness and paralysis. In the United States, from 1999-2005, there have been nearly 20,000 confirmed cases with 752 deaths. Severe neurological disease including meningitis or encephalitis was seen in about 30% of confirmed cases. To address the need for new and better vaccines for flavivirus diseases we have developed a method to produce genetically engineered, 'pseudo-infectious' flaviviruses (RepliVAX) that offer great promise as vaccine candidates. RepliVAX undergo a limited replication cycle, producing large amounts of a highly immunogenic subviral immunogen. We have shown that WNV RepliVAX is extremely safe and does not cause disease in baby mice or adult mice, and that mice inoculated with the WNV RepliVAX produce high titers of WNV-neutralizing antibodies and are completely protected from WNV -induced encephalitis. Thus, RepliVAXs are ideal safe and effective vaccine candidates. We will test the safety, potency, and efficacy of the WNV RepliVAX vaccine in non-human primates. Successfully completion of these studies will provide critical information for the advancement of our WNV vaccine candidates, and will help to assure the suitability of the RepliVAX platform for producing vaccines to protect against other flavivirus diseases.
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