Capturing the Natural Diversity of the Human Antibody Response against Vaccinia Virus ▿
| Autor: | Allan Jensen, Søren Bregenholt, Jackie Duggan, Irene Naylor, Hansen Margit H, Søren Kofoed Rasmussen, Tine Rugh Poulsen, Linda Easterbrook, Lucilla Steinaa, Johan Lantto, Mike Dennis, John Haurum |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
viruses
Immunology Molecular Sequence Data Blood Donors Vaccinia virus Biology Antibodies Viral Microbiology chemistry.chemical_compound Mice Antigen Antibody Specificity Virology medicine Smallpox Animals Humans Poxviridae Orthopoxvirus Smallpox vaccine Antigens Viral Mice Inbred BALB C Vaccines Synthetic Vaccination virus diseases Genetic Variation Sequence Analysis DNA medicine.disease biology.organism_classification Antibodies Neutralizing Chordopoxvirinae chemistry Insect Science Immunoglobulin G Antibody Formation Pathogenesis and Immunity Female Vaccinia Smallpox Vaccine |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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