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

Abstract

BackgroundPreviously 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).ResultsHere, 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.ConclusionsA 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.

Effects of Postchallenge Administration of ST-246 on Dissemination of IHD-J-Luc Vaccinia Virus in Normal Mice and in Immune-Deficient Mice Reconstituted with T Cells

“…In addition to fluxes in organs, we used dorsal images of infected mice to count poxes on mouse tails (Table 2) (22). No poxes were detected in mice prior to day 3 postinfection (data not shown).…”

“…In all calculations, the background bioluminescence was subtracted from experimental values. Poxvirus lesions were counted on mouse tails using dorsal images as previously described (22).…”

Postchallenge Administration of Brincidofovir Protects Healthy and Immune-Deficient Mice Reconstituted with Limited Numbers of T Cells from Lethal Challenge with IHD-J-Luc Vaccinia Virus

“…The background bioluminescence was determined using images of D-luciferin-injected animals acquired 1 day prior to infection. Pox lesions were counted on mouse tails using dorsal images, as previously described (34).…”

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

“…Although still controversial, the critical role of the antigen-specific humoral response against OPXV has already been described (Edghill-Smith et al, 2005;Panchanathan et al, 2006), and passive transfer of VV-specific sera was shown to confer protection in both mice and monkeys (Golden et al, 2011). In the present study, although the magnitude of the humoral response was highly variable, a correlation with mice survival was shown soon after the first immunization.…”