Quantitative bioimaging of WRvFire and of IHDJ-Luc vaccinia virus dissemination in mice and the effects of prophylactic and therapeutic treatments with IgG and antiviral.

Abstract Whole body bioluminescence imaging was employed to test the effects of IgG-based therapies and Cidofovir on lethality and virus dissemination in BALB/c mice challenged intranasally with 10^5 pfu of recombinant vaccinia viruses (VV) expressing luciferase, WRvFire or IHDJ-Luc. Both viruses induced lethality within 6-8 days, with slightly different kinetics of replication in internal organs. Using statistical analysis of 80 animals/group we determined that replication of IHDJ-Luc (increased Extracellular Enveloped Virion compared to WR) rose faster and peaked earlier than WRvFire (predominantly Intracellular Mature Virion) in the liver and spleen. In the nasal cavity, WRvFire persisted at significantly higher levels than IHDJ-Luc. Vaccinia immunoglobulin for intravenous injection (VIGIV) administered at day -2 protected 100% of animals from WRvFire and IHDJ-Luc infections. Sym002 (26 anti-vaccinia human mAbs) completely protected mice from both challenges at 300-fold lower dose than VIGIV. A single treatment of Cidofovir (100 mg/kg) at day 1, 2, or 3 p.i. fully protected mice from WRvFire challenge. Complete protection conferred by treatments correlated with significant reductions in bioluminescence in nasal cavity or lungs and in both the liver and spleen between days 1-5. Our data demonstrated that despite some differences observed in the kinetics of VV dissemination, infections with these viruses were similarly susceptible to prophylactic and therapeutic treatments.