Therapeutic Potential of Vaccinia Hyper Immune Sera in Mouse Models of Lethal Orthopoxviruses Infection

Vaccinia Immune Globulin (VIG) is currently used to treat severe complications of smallpox vaccines. In this study we compare the therapeutic potential of vaccinia virus rabbit hyper immune sera (RHIS) with that of human VIG. The clearance rate of RHIS from mouse circulation is only slightly slower than that of VIG (t 1/2=10 and 7.5 days respectively). Like VIG, passively administered RHIS can protect mice against lethal respiratory and dermal Ectromelia virus (ECTV) challenge. Administration of both homologous (anti ECTV) and heterologous (anti VACV-WR or VACV-Lister) anti-sera conferred efficient protection against a subsequent lethal respiratory ECTV challenge. These observations formed the basis for passive cross protection studies against ECTV, conducted in mice. RHIS conferred better protection as compared to VIG as a result of its better specific activity which is about 100 folds higher than that of VIG, allowing for significant protection even if administered 5 days post infection. This study emphasizes the advantage of a hyper immune product and validates the potential use of VIG and other antibody based therapeutics, not only as prophylactic measures against post-vaccination complications but also for post-exposure treatment of smallpox disease.