title: Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.
abstract: A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the 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 virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. 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 and combination therapies and to provide further insights into the pathogenesis and treatment of PV.
authors.affiliation: Laboratory of Plasma Derivatives, Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA. Robert.Fisher@fda.hhs.gov
authors.forename: R W
authors.initials: RW
authors.lastname: Fisher
authors.forename: J L
authors.initials: JL
authors.lastname: Reed
authors.forename: P J
authors.initials: PJ
authors.lastname: Snoy
authors.forename: M G
authors.initials: MG
authors.lastname: Mikolajczyk
authors.forename: M
authors.initials: M
authors.lastname: Bray
authors.forename: D E
authors.initials: DE
authors.lastname: Scott
authors.forename: M C
authors.initials: MC
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D063065:Organophosphonates / Q000627:therapeutic use; D056990:Post-Exposure Prophylaxis; D012867:Skin / Q000473:pathology / Q000821:virology; D015996:Survival Rate; D014611:Vaccination; D014615:Vaccinia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D007136:Immunoglobulins; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir