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Program Overview:
Hemorrhagic fever with renal syndrome occurs predominantly in soldiers, in a sporadic or epidemic form. Because of the course of disease and potentially lethal outcome, the disease has a considerable impact on the field task performance and combat readiness of military units and is of great importance for a military community. Accommodation in permanent buildings with appropriate common and personal hygiene standards is recommended, however, not possible during major operations in the field as shown during the Korean conflict. More than 3,000 United Nation soldiers contracted Korean Hemorrhagic Fever. The etiologic agent for Korean Hemorrhagic Fever was identified in 1979 as a hantavirus of the Bunyaviridae family whose hosts are rodents. Disease is transmitted by aerosolization of urine, feces and saliva present in nests and infested dwellings. Subsequently it has been demonstrated that a large number of related hemorrhagic viruses can also cause a similar disease. The diseases caused by these viruses are commonly associated with renal disease. The WHO renamed this group of diseases as Hemorrhagic Fevers with Renal Syndrome. The different members of this group cause severe to mild disease with 5-15% fatality rate in the former and <1% in the latter group.

HFRS continues to be a threat to US forces. Eighteen U.S. Marines contracted HFRS during training exercises in Korea in 1987; two of them died. Thirteen U.S. Army Reserve soldiers were diagnosed with HFRS in Germany in 1990 in the first recognized outbreak of this disease among soldiers serving in Europe. The Korean army experiences a significant number of KHF cases each year; U.S. forces in Korea experience several cases annually. Historically, HFRS-like disease in military populations have been reported as far back as the American Civil War. HFRS affected large numbers of foreign troops during WWI and WWII. Nonimmunized service members deployed to HFRS-endemic regions are at risk particularly when operating in the field where the rodent host of the virus is common. The resulting disease, especially during large outbreaks of the severe forms of the disease can disrupt operations and will put a severe strain on medical care and logistics where renal failure requires renal dialysis equipment to maintain electrolyte balance and reduction in shock and major organ failure.

Task Area T has produced molecular vaccines (DNA vaccine plasmids) that have shown protective efficacy in animals for several HFRS and HPS hantaviruses (e.g. Hantaan virus, Puumala virus, Seoul virus, Andes virus, and Sin Nombre virus), Lassa virus, and Rift Valley fever virus. South American arenavirus DNA vaccines have been shown to elicit neutralizing antibodies in rabbits. Protection studies are scheduled for FY13. The Crimean Congo Hemorrhagic fever virus DNA vaccine remains a technical challenge. Antibody has been shown to be sufficient to protect against both HFRS and HPS hantaviruses, but not Lassa virus. The first-ever animal model to mimic human disease was developed (i.e., Andes virus in Syrian hamsters).

The ultimate aim of the Lethal Virus Countermeasures Program Area is to deliver medical countermeasures to protect military personnel (and civilians) from diseases caused by hantaviruses and other highly lethal viruses that pose a natural threat to personnel deployed in disease-endemic environments. The viruses of interest fall within two taxonomic families, the Bunyavirida and Arenavirida. The overall strategy for accomplishing the goals of this Task Area involves "proof of concept" studies that provide candidate medical countermeasures for relatively rare but highly lethal diseases of military importance. DNA vaccine technology is used to identify protective immunogens for use in molecular vaccines, to produce pseudovirions for rapid neutralization assays and as a technology to produce protective and diagnostic antibodies. Unique animal models are developed for investigating the pathogenesis underlying these viral diseases, and for testing vaccines and other intervention strategies. A vaccine to prevent HFRS in deployed service members is a priority of this program.

HIV | Flavivirus Vaccines | Lethal Virus Countermeasures