Quantitative bioimaging of the WR and IHDJ vaccinia virus dissemination and the effects of prophylactic immunoglobulin treatments (128.23)

Abstract Protection from lethal challenge with recombinant WR-Luciferase (TK+) and IHDJ-Luciferase (TK+) vaccinia viruses (VV) was studied by detecting firefly luciferase activity in live Balb/c mice using IVIS technology. High correlation (R2=0.8-0.9) was observed between viral loads in the organs measured by plaque assay and bioluminescence. WR- and IHDJ VV that generate predominantly IMV and EEV forms, respectively, induced lethality within 8-10 days after intranasal challenge with 10^5 pfu yet their dissemination and susceptibility to therapies differed. WR persisted at significantly higher levels than IHDJ at the site of challenge, while IHDJ replicated better in the liver in agreement with the roles of EEV and IMV in host dissemination and inter host transmission. Vaccinia immunoglobulin (VIGIV) at Day -2 completely protected from the WR but not from IHDJ challenge. Sym002, a mixture of 26 human anti-vaccinia mAbs (Symphogen, Denmark), completely protected from WR challenge at 1000 lower dose than VIGIV, but only partially protected from IHDJ. Protection by Sym002 correlated with a significantly reduced flux at the nasopharyngeal area and in the liver. Importantly, our study detected significantly higher bioluminescence at the nasopharyngeal area and in the lungs in non-survivors than in survivors suggesting that bioimaging can substitute for lethality endpoint for evaluation of anti-smallpox treatments.