Scientific Publications by FDA Staff
Clin Vaccine Immunol 2011 Jan;18(1):67-74
Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.
Fisher RW, Reed JL, Snoy PJ, Mikolajczyk MG, Bray M, Scott DE, Kennedy MC
A recently reported case of progressive vaccinia (PV) in an immune compromised patient has refocused attention on this condition. Uniformly fatal prior to licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola release would inevitably result in exposure of immune compromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if untreated. Post-exposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most animals, even when initiated seven days post-infection. These results support the possibility that combination treatments may be effective in humans, and support using this SCID model of PV to test new antibody therapies, combination therapies, and to provide further insights on pathogenesis and treatment of PV.
|Category: Journal Article|
|PubMed ID: #21106779||DOI: 10.1128/CVI.00280-10|
|PubMed Central ID: #PMC3019770|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-03||Entry Last Modified: 2012-08-29|