title: Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.
abstract: Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702, USA. jay.hooper@amedd.army.mil
authors.forename: J W
authors.initials: JW
authors.lastname: Hooper
authors.forename: E
authors.initials: E
authors.lastname: Thompson
authors.forename: C
authors.initials: C
authors.lastname: Wilhelmsen
authors.forename: M
authors.initials: M
authors.lastname: Zimmerman
authors.forename: M Ait
authors.initials: MA
authors.lastname: Ichou
authors.forename: S E
authors.initials: SE
authors.lastname: Steffen
authors.forename: C S
authors.initials: CS
authors.lastname: Schmaljohn
authors.forename: A L
authors.initials: AL
authors.lastname: Schmaljohn
authors.forename: P B
authors.initials: PB
authors.lastname: Jahrling
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D045908:Mpox, Monkeypox / Q000517:prevention & control*; D008993:Monkeypox virus / Q000472:pathogenicity*; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: C110360:A27L protein, Orthopoxvirus; C446940:A33R protein, Vaccinia virus; D000914:Antibodies, Viral; C087715:L1R protein, Vaccinia virus; D008562:Membrane Glycoproteins; D012900:Smallpox Vaccine; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C074512:42kDa protein, Vaccinia virus