Army

DNA vaccine for hemorrhagic fever with renal syndrome

Creates neutralizing antibodies against four hantavirus strains

Medical & Biotechnology

Hantaviruses are maintained in rodent reservoirs and are usually transmitted to humans in aerosols of rodent excreta

The Hantavirus genus of the family Bunyaviridae includes a number of rodent-borne viruses that can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). At least four hantaviruses cause HFRS: Hantaan (HTNV), Seoul (SEOV), Dobrava (DOBV), and Puumala (PUUV). HFRS presents with sudden fever, chills, nausea, headache, and backache. Early symptoms of severe HFRS often also include facial flushing, conjunctivitis, and petechial rash. Death can occur due to vascular leakage leading to low blood pressure, acute shock, and renal failure. Like Dobrava virus, Hantaan virus has a mortality rate of 10 to 12 percent. There are no FDA-licensed vaccines for preventing hantavirus-associated HFRS, but an inactivated, rodent brain-derived HTNV vaccine is commercially available in Korea. Several inactivated cell culture-derived HTNV and SEOV vaccines also have been developed in China.

Despite the use of these vaccines for more than a decade, HFRS remains a significant public health threat in Asia, with thousands of hospitalized cases reported each year in China. Several hundred to thousands of HFRS cases due to PUUV or DOBV infections are reported each year in Europe, Scandinavia, and Russia. Inactivated vaccines have not been developed in Europe, in part because PUUV is difficult to grow in cell culture to high enough titers for scale-up, and rodent brain-derived vaccines are not considered desirable. Moreover, because DOBV and PUUV both cause HFRS in the same geographic region, and because there is little or no cross-protective immunity between PUUV and the other HFRS-causing hantaviruses, a comprehensive vaccine for European HFRS will need to elicit protective immunity to both viruses.

To address the above, Army researchers have developed a combination vaccine to protect against HFRS. The invention consists of an optimized HTNV M-segment vaccine, which solves the problem of interference in the bivalent vaccine. The new composition can be mixed with a similarly optimized PUUV-based vaccine to elicit neutralizing antibodies against both viruses. The invention provides a safe, economical, flexible, and effective vaccine for the protection of humans from HFRS caused by infection with HTNV, SEOV, PUUV and/or DOBV.

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