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Journal of Virology, September 2001, p. 8469-8477, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8469-8477.2001

DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Elicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys

J. W. Hooper,* D. M. Custer, E. Thompson, and C. S. Schmaljohn

Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702

Received 12 March 2001/Accepted 11 June 2001

Four hantaviruses---Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus---are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.


* Corresponding author. Mailing address: Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD 21702. Phone: (301) 619-4101. Fax: (301) 619-2439. E-mail: Jay.Hooper{at}det.amedd.army.mil.


Journal of Virology, September 2001, p. 8469-8477, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8469-8477.2001



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