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.
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.
Hooper
J W
JW
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702, USA. Jay.Hooper@det.amedd.army.mil
Custer
D M
DM
Thompson
E
E
Schmaljohn
C S
CS
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003429:Cross Reactions; D004279:DNA, Viral / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D005814:Genes, Viral; D018063:Hantaan virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006480:Hemorrhagic Fever with Renal Syndrome / Q000517:prevention & control* / Q000821:virology; D008253:Macaca mulatta; D009500:Neutralization Tests; D011323:Primates; D014611:Vaccination; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C104008:glycoprotein G1, Hantavirus; C090197:glycoprotein G2, Hantavirus