1. Engineering, expression in transgenic plants and characterisation of E559, a rabies virus-neutralising monoclonal antibody.
- Author
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van Dolleweerd CJ, Teh AY, Banyard AC, Both L, Lotter-Stark HC, Tsekoa T, Phahladira B, Shumba W, Chakauya E, Sabeta CT, Gruber C, Fooks AR, Chikwamba RK, and Ma JK
- Subjects
- Animals, Antibodies, Monoclonal genetics, Antibodies, Viral genetics, Cricetinae, Disease Models, Animal, Humans, Mesocricetus, Mice, Plants, Genetically Modified, Rabies prevention & control, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins therapeutic use, Nicotiana genetics, Antibodies, Monoclonal biosynthesis, Antibodies, Monoclonal therapeutic use, Antibodies, Viral biosynthesis, Antibodies, Viral therapeutic use, Rabies virus immunology
- 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., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)
- Published
- 2014
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