Capturing the natural diversity of the human antibody response against vaccinia virus

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 numbe...

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Main Authors: Lantto, J., Hansen, M.H., Rasmussen, S.K., Steinaa, Lucilla, Poulsen, T.R., Duggan, J., Dennis, M., Naylor, I., Easterbrook, L., Bregenholt, S., Haurum, J., Jensen, A.
Format: Journal Article
Language:Inglés
Published: American Society for Microbiology 2011
Subjects:
Online Access:https://hdl.handle.net/10568/35251
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author Lantto, J.
Hansen, M.H.
Rasmussen, S.K.
Steinaa, Lucilla
Poulsen, T.R.
Duggan, J.
Dennis, M.
Naylor, I.
Easterbrook, L.
Bregenholt, S.
Haurum, J.
Jensen, A.
author_browse Bregenholt, S.
Dennis, M.
Duggan, J.
Easterbrook, L.
Hansen, M.H.
Haurum, J.
Jensen, A.
Lantto, J.
Naylor, I.
Poulsen, T.R.
Rasmussen, S.K.
Steinaa, Lucilla
author_facet Lantto, J.
Hansen, M.H.
Rasmussen, S.K.
Steinaa, Lucilla
Poulsen, T.R.
Duggan, J.
Dennis, M.
Naylor, I.
Easterbrook, L.
Bregenholt, S.
Haurum, J.
Jensen, A.
author_sort Lantto, J.
collection Repository of Agricultural Research Outputs (CGSpace)
description 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.
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spelling CGSpace352512024-08-27T10:36:04Z Capturing the natural diversity of the human antibody response against vaccinia virus Lantto, J. Hansen, M.H. Rasmussen, S.K. Steinaa, Lucilla Poulsen, T.R. Duggan, J. Dennis, M. Naylor, I. Easterbrook, L. Bregenholt, S. Haurum, J. Jensen, A. animal diseases vaccines 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. 2011-02-15 2014-04-14T10:55:38Z 2014-04-14T10:55:38Z Journal Article https://hdl.handle.net/10568/35251 en Open Access American Society for Microbiology Lantto, J., Hansen, M.H., Rasmussen, S.K., Steinaa, L., Poulsen, T.R., Duggan, J., Dennis, M., Naylor, I., Easterbrook, L., Bregenholt, S., Haurum, J. and Jensen, A. 2010. Capturing the natural diversity of the human antibody response against vaccinia virus 85(4): 1820 - 1833
spellingShingle animal diseases
vaccines
Lantto, J.
Hansen, M.H.
Rasmussen, S.K.
Steinaa, Lucilla
Poulsen, T.R.
Duggan, J.
Dennis, M.
Naylor, I.
Easterbrook, L.
Bregenholt, S.
Haurum, J.
Jensen, A.
Capturing the natural diversity of the human antibody response against vaccinia virus
title Capturing the natural diversity of the human antibody response against vaccinia virus
title_full Capturing the natural diversity of the human antibody response against vaccinia virus
title_fullStr Capturing the natural diversity of the human antibody response against vaccinia virus
title_full_unstemmed Capturing the natural diversity of the human antibody response against vaccinia virus
title_short Capturing the natural diversity of the human antibody response against vaccinia virus
title_sort capturing the natural diversity of the human antibody response against vaccinia virus
topic animal diseases
vaccines
url https://hdl.handle.net/10568/35251
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