Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3

Autor: Baby Phahladira, Charles E. Rupprecht, Herta Steinkellner, Michael H. Pauly, Tsepo L. Tsekoa, Steve Hume, Claude T. Sabeta, Josh Morton, Larry Zeitlin, Kevin J. Whaley, Ereck Chakauya, Wonderful Shumba, Stoyan Stoychev, Therese Lotter-Stark, Rachel Chikwamba, Sindisiwe G. Buthelezi
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
RNA viruses
Viral Diseases
Glycosylation
Physiology
medicine.medical_treatment
viruses
Glycobiology
Nicotiana benthamiana
Gene Expression
lcsh:Medicine
medicine.disease_cause
Pathology and Laboratory Medicine
Antibodies
Viral
Biochemistry
Geographical locations
law.invention
South Africa
0302 clinical medicine
law
Immune Physiology
Zoonoses
Medicine and Health Sciences
030212 general & internal medicine
Post-Translational Modification
Cloning
Molecular
lcsh:Science
Flowering Plants
Mammals
Multidisciplinary
Immune System Proteins
Antibodies
Monoclonal
Plants
Plants
Genetically Modified
Recombinant Proteins
Infectious Diseases
Medical Microbiology
Viral Pathogens
Viruses
Vertebrates
Recombinant DNA
Hamsters
Female
Antibody
Pathogens
Research Article
Neglected Tropical Diseases
Nicotiana
medicine.drug_class
Rabies
Immunology
Genetic Vectors
Biology
Monoclonal antibody
Microbiology
Rodents
Antibodies
03 medical and health sciences
Rabies Virus
Dogs
In vivo
Neutralization Tests
Tobacco
medicine
Animals
Post-exposure prophylaxis
Microbial Pathogens
Biology and life sciences
Mesocricetus
Rabies virus
lcsh:R
Organisms
Immunization
Passive
Proteins
biology.organism_classification
medicine.disease
Tropical Diseases
Virology
Survival Analysis
030104 developmental biology
Rabies Vaccines
Agrobacterium tumefaciens
Amniotes
Africa
biology.protein
Lyssavirus
lcsh:Q
People and places
Zdroj: PLoS ONE, Vol 11, Iss 7, p e0159313 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Rabies is a neglected zoonotic disease that has no effective treatment after onset of illness. However the disease can be prevented effectively by prompt administration of post exposure prophylaxis which includes administration of passive immunizing antibodies (Rabies Immune Globulin, RIG). Currently, human RIG suffers from many restrictions including limited availability, batch-to batch inconsistencies and potential for contamination with blood-borne pathogens. Anti-rabies monoclonal antibodies (mAbs) have been identified as a promising alternative to RIG. Here, we applied a plant-based transient expression system to achieve rapid, high level production and efficacy of the two highly potent anti-rabies mAbs E559 and 62-71-3. Expression levels of up to 490 mg/kg of recombinant mAbs were obtained in Nicotiana benthamiana glycosylation mutants by using a viral based transient expression system. The plant-made E559 and 62-71-3, carrying human-type fucose-free N-glycans, assembled properly and were structurally sound as determined by mass spectrometry and calorimetric density measurements. Both mAbs efficiently neutralised diverse rabies virus variants in vitro. Importantly, E559 and 62-71-3 exhibited enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. Collectively, our results provide the basis for the development of a multi-mAb based alternative to RIG.
Databáze: OpenAIRE
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