title: Effective post-exposure protection against lethal orthopoxviruses infection by vaccinia immune globulin involves induction of adaptive immune response.
abstract: The therapeutic potential of human vaccinia immunoglobulin (VIG) in orthopoxvirus infection was examined using two mouse models for human poxvirus, based on Ectromelia virus and Vaccinia Western Reserve (WR) respiratory infections. Despite the relatively fast clearance of human VIG from mice circulation, a single VIG injection protected immune-competent mice against both infections. Full protection against lethal Ectromelia virus infection was achieved by VIG injection up to one day post-exposure, and even injection of VIG two or three days post-infection conferred solid protection (60-80%). Nevertheless, VIG failed to protect VACV-WR challenged immune-deficient mice, even though repeated injections prolonged SCID mice survival. These results suggest the involvement of host immunity in protection. VIG provides the initial protective time-window allowing induction of the adaptive response required to achieve complete protection. Additionally, VIG can be administered in conjunction with active Vaccinia-Lister vaccination. Vaccine efficiency is not impaired, providing a non-prohibitive VIG dose is used. Thus, VIG can be used as a prophylactic measure against post-vaccinal complications but could also serve for post-exposure treatment against smallpox.
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Israel. shlomol@iibr.gov.il
authors.forename: Shlomo
authors.initials: S
authors.lastname: Lustig
authors.forename: Galia
authors.initials: G
authors.lastname: Maik-Rachline
authors.forename: Nir
authors.initials: N
authors.lastname: Paran
authors.forename: Sharon
authors.initials: S
authors.lastname: Melamed
authors.forename: Tomer
authors.initials: T
authors.lastname: Israely
authors.forename: Noam
authors.initials: N
authors.lastname: Erez
authors.forename: Nadav
authors.initials: N
authors.lastname: Orr
authors.forename: Shaul
authors.initials: S
authors.lastname: Reuveny
authors.forename: Arie
authors.initials: A
authors.lastname: Ordentlich
authors.forename: Orgad
authors.initials: O
authors.lastname: Laub
authors.forename: Avigdor
authors.initials: A
authors.lastname: Shafferman
authors.forename: Baruch
authors.initials: B
authors.lastname: Velan
mesh_terms: D000818:Animals; D004480:Ectromelia / Q000276:immunology / Q000517:prevention & control; D004481:Ectromelia virus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018155:Orthopoxvirus; D011213:Poxviridae Infections / Q000517:prevention & control*; D012137:Respiratory System / Q000473:pathology; D014615:Vaccinia / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007136:Immunoglobulins