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Journal of Virology, September 2001, p. 8469-8477, Vol. 75, No. 18
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
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
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.
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