title: Construction and nonclinical testing of a Puumala virus synthetic M gene-based DNA vaccine.
abstract: Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-length M segment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Brocato
authors.forename: M J
authors.initials: MJ
authors.lastname: Josleyn
authors.forename: V
authors.initials: V
authors.lastname: Wahl-Jensen
authors.forename: C S
authors.initials: CS
authors.lastname: Schmaljohn
authors.forename: J W
authors.initials: JW
authors.lastname: Hooper
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003429:Cross Reactions; D004279:DNA, Viral / Q000276:immunology; D006476:Orthohantavirus / Q000276:immunology; D018778:Hantavirus Infections / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology; D009500:Neutralization Tests; D029262:Puumala virus / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins; D014765:Viral Vaccines