Scientific Publications by FDA Staff

J Virol 2011 Sep;85(17):9147-58

Passive immunotherapies protect WRvFire and IHD-J-Luc vaccinia virus infected mice from lethality by reducing viral loads in the upper respiratory tract and internal organs.

Zaitseva M, Kapnick SM, Meseda CA, Shotwell E, King LR, Manischewitz J, Scott J, Kodihalli S, Merchlinsky M, Nielsen H, Lantto J, Weir JP, Golding H

Whole body bioimaging was employed to study the effects of passive immunotherapies on lethality and viral dissemination in BALB/c mice challenged with recombinant vaccinia viruses expressing luciferase. WRvFire and IHD-J-Luc vaccinia viruses induced lethality with similar time to death following intranasal infection, but WRvFire replicated at higher levels than IHD-J-Luc in the upper and lower respiratory tract. Three types of therapies were tested: licensed human anti-vaccinia immune globulin VIGIV; recombinant VIG (rVIG; Symphogen, Denmark), an investigational product containing a mixture of 26 human monoclonal antibodies (HuMAbs) against MV and EV virions, and HuMAb compositions targeting subsets of MV or EV proteins. Bioluminescence recorded daily showed that pretreatment with VIGIV (30 mg) or with rVIG (100 ¿g) on day -2 protected mice from death, but did not prevent viral replication at the site of inoculation and dissemination to internal organs. Compositions containing HuMAbs against MV or EV proteins were protective in both infection models at 100 ¿g per animal but at 30 ¿g, only anti-EV antibodies conferred protection. Importantly, t statistic of the mean total fluxes revealed that viral loads in surviving mice were significantly reduced in at least 3 sites for 3 consecutive days (day 3-5) post challenge, while significant reduction for 1-2 days in any individual site did not confer protection. Our data suggest that reduction of viral replication at multiple sites including respiratory tract, spleen and liver, as monitored by whole body bioluminescence can be used to predict the effectiveness of passive immunotherapies in mouse models.