title: Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease.
abstract: BACKGROUND
  Previously we demonstrated that DNA vaccination of nonhuman primates (NHP) with a small subset of vaccinia virus (VACV) immunogens (L1, A27, A33, B5) protects against lethal monkeypox virus challenge. The L1 and A27 components of this vaccine target the mature virion (MV) whereas A33 and B5 target the enveloped virion (EV).
  
  
  RESULTS
  Here, we demonstrated that the antibodies produced in vaccinated NHPs were sufficient to confer protection in a murine model of lethal Orthopoxvirus infection. We further explored the concept of using DNA vaccine technology to produce immunogen-specific polyclonal antibodies that could then be combined into cocktails as potential immunoprophylactic/therapeutics. Specifically, we used DNA vaccines delivered by muscle electroporation to produce polyclonal antibodies against the L1, A27, A33, and B5 in New Zealand white rabbits. The polyclonal antibodies neutralized both MV and EV in cell culture. The ability of antibody cocktails consisting of anti-MV, anti-EV, or a combination of anti-MV/EV to protect BALB/c mice was evaluated as was the efficacy of the anti-MV/EV mixture in a mouse model of progressive vaccinia. In addition to evaluating weight loss and lethality, bioimaging technology was used to characterize the spread of the VACV infections in mice. We found that the anti-EV cocktail, but not the anti-MV cocktail, limited virus spread and lethality.
  
  
  CONCLUSIONS
  A combination of anti-MV/EV antibodies was significantly more protective than anti-EV antibodies alone. These data suggest that DNA vaccine technology could be used to produce a polyclonal antibody cocktail as a possible product to replace vaccinia immune globulin.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Golden
authors.forename: Marina
authors.initials: M
authors.lastname: Zaitseva
authors.forename: Senta
authors.initials: S
authors.lastname: Kapnick
authors.forename: Robert W
authors.initials: RW
authors.lastname: Fisher
authors.forename: Malgorzata G
authors.initials: MG
authors.lastname: Mikolajczyk
authors.forename: John
authors.initials: J
authors.lastname: Ballantyne
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.forename: Jay W
authors.initials: JW
authors.lastname: Hooper
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile; D000914:Antibodies, Viral / Q000008:administration & dosage*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001835:Body Weight; D004195:Disease Models, Animal; D018274:Electroporation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D009132:Muscles / Q000276:immunology; D009500:Neutralization Tests; D011817:Rabbits; D012900:Smallpox Vaccine / Q000235:genetics* / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control*; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014771:Virion / Q000187:drug effects / Q000276:immunology
chemical_list: D000910:Antibodies, Heterophile; D000914:Antibodies, Viral; D000956:Antigens, Viral; D012900:Smallpox Vaccine; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins