title: Capturing the natural diversity of the human antibody response against vaccinia virus.
abstract: The eradication of smallpox (variola) and the subsequent cessation of routine vaccination have left modern society vulnerable to bioterrorism employing this devastating contagious disease. The existing, licensed vaccines based on live vaccinia virus (VACV) are contraindicated for a substantial number of people, and prophylactic vaccination of large populations is not reasonable when there is little risk of exposure. Consequently, there is an emerging need to develop efficient and safe therapeutics to be used shortly before or after exposure, either alone or in combination with vaccination. We have characterized the human antibody response to smallpox vaccine (VACV Lister) in immunized volunteers and isolated a large number of VACV-specific antibodies that recognize a variety of different VACV antigens. Using this broad antibody panel, we have generated a fully human, recombinant analogue to plasma-derived vaccinia immunoglobulin (VIG), which mirrors the diversity and specificity of the human antibody immune response and offers the advantage of unlimited supply and reproducible specificity and activity. The recombinant VIG was found to display a high specific binding activity toward VACV antigens, potent in vitro VACV neutralizing activity, and a highly protective efficacy against VACV challenge in the mouse tail lesion model when given either prophylactically or therapeutically. Altogether, the results suggest that this compound has the potential to be used as an effective postexposure prophylaxis or treatment of disease caused by orthopoxviruses.
authors.affiliation: Symphogen A/S, Elektrovej, Building 375, DK-2800 Lyngby, Denmark. jol@symphogen.com
authors.forename: Johan
authors.initials: J
authors.lastname: Lantto
authors.forename: Margit
authors.initials: M
authors.lastname: Haahr Hansen
authors.forename: Søren Kofoed
authors.initials: SK
authors.lastname: Rasmussen
authors.forename: Lucilla
authors.initials: L
authors.lastname: Steinaa
authors.forename: Tine R
authors.initials: TR
authors.lastname: Poulsen
authors.forename: Jackie
authors.initials: J
authors.lastname: Duggan
authors.forename: Mike
authors.initials: M
authors.lastname: Dennis
authors.forename: Irene
authors.initials: I
authors.lastname: Naylor
authors.forename: Linda
authors.initials: L
authors.lastname: Easterbrook
authors.forename: Søren
authors.initials: S
authors.lastname: Bregenholt
authors.forename: John
authors.initials: J
authors.lastname: Haurum
authors.forename: Allan
authors.initials: A
authors.lastname: Jensen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000917:Antibody Formation; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001782:Blood Donors; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D012899:Smallpox / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D014616:Vaccinia virus / Q000145:classification / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic