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

Johan Lantto, Margit Haahr Hansen, Søren Kofoed Rasmussen, Lucilla Steinaa, Tine R. Poulsen, Jacqueline Duggan, Michael Dennis, Irene Naylor, Linda Easterbrook, Søren Bregenholt, John Haurum, Allan Jensen

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1820-1833
Number of pages14
JournalJournal of Virology
Volume85
Issue number4
DOIs
Publication statusPublished - Feb 2011

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