Academic Journals Database
Disseminating quality controlled scientific knowledge

Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease

ADD TO MY LIST
 
Author(s): Golden Joseph | Zaitseva Marina | Kapnick Senta | Fisher Robert | Mikolajczyk Malgorzata | Ballantyne John | Golding Hana | Hooper Jay

Journal: Virology Journal
ISSN 1743-422X

Volume: 8;
Issue: 1;
Start page: 441;
Date: 2011;
Original page

Keywords: Smallpox | vaccinia immunoglobulin | monoclonal antibody | passive protection | DNA vaccine | polyclonal antibody | bioluminescence

ABSTRACT
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.

Tango Jona
Tangokurs Rapperswil-Jona

     Affiliate Program