title: Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates.
abstract: Two major infectious forms of vaccinia virus (VACV) have been described: the intracellular mature virion (IMV), and the extracellular enveloped virion (EEV). Due to their stability in the environment, IMVs play a predominant role in host-to-host transmission, whereas EEVs play an important role in dissemination within the host. In a previous report, we demonstrated that mice vaccinated with VACV L1R (IMV immunogen) and A33R (EEV immunogen) were protected from a lethal poxvirus challenge. Vaccination with a combination of both genes conferred greater protection than either gene alone, suggesting that an immune response against both IMV and EEV is advantageous. Here, we report that in mice individually administered DNA vaccines with two different VACV immunogens, A27L (IMV immunogen) or B5R (EEV immunogen), failed to significantly protect; however, vaccination with a combination of both genes conferred a high level of protection. Mice were completely protected when vaccinated with a combination of four VACV genes (A27L + A33R + L1R + B5R). Rhesus macaques vaccinated with this four-gene-combination developed appropriate antibody responses to each protein. Antibody responses elicited by this vaccine cross-reacted with monkeypox virus orthologous proteins. These data indicate that a gene-based vaccine comprised of the VACV A27L + A33R + L1R + B5R genes may be a useful candidate to protect against other orthopoxviruses, including those that cause monkeypox and smallpox.
authors.affiliation: Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. jay.hooper@amedd.army.mil
authors.forename: J W
authors.initials: JW
authors.lastname: Hooper
authors.forename: D M
authors.initials: DM
authors.lastname: Custer
authors.forename: E
authors.initials: E
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014615:Vaccinia / Q000517:prevention & control*; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / 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; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C074512:42kDa protein, Vaccinia virus