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J Infect Dis. 2014 Jul 15;210(2):200-8. doi: 10.1093/infdis/jiu085. Epub 2014 Feb 7.

Engineering, expression in transgenic plants and characterisation of E559, a rabies virus-neutralising monoclonal antibody.

Author information

1
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
2
Wildlife Zoonoses and Vector Borne Disease Research Group, Animal Health and Veterinary Laboratories Agency (AHVLA), Surrey, United Kingdom.
3
Council for Scientific and Industrial Research (CSIR), Biosciences, Pretoria, South Africa.
4
Agricultural Research Council-Onderstepoort Veterinary Institute (ARC-OVI), OIE Rabies Reference Laboratory, Onderstepoort, Pretoria, South Africa.
5
Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.

Abstract

Rabies post-exposure prophylaxis (PEP) currently comprises administration of rabies vaccine together with rabies immunoglobulin (RIG) of either equine or human origin. In the developing world, RIG preparations are expensive, often in short supply, and of variable efficacy. Therefore, we are seeking to develop a monoclonal antibody cocktail to replace RIG. Here, we describe the cloning, engineering and production in plants of a candidate monoclonal antibody (E559) for inclusion in such a cocktail. The murine constant domains of E559 were replaced with human IgG1κ constant domains and the resulting chimeric mouse-human genes were cloned into plant expression vectors for stable nuclear transformation of Nicotiana tabacum. The plant-expressed, chimeric antibody was purified and biochemically characterized, was demonstrated to neutralize rabies virus in a fluorescent antibody virus neutralization assay, and conferred protection in a hamster challenge model.

KEYWORDS:

Nicotiana tabacum; RIG; monoclonal antibody; post-exposure prophylaxis; rabies

PMID:
24511101
PMCID:
PMC4073784
DOI:
10.1093/infdis/jiu085
[Indexed for MEDLINE]
Free PMC Article
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