Purification of yellow fever virus produced in Vero cells for inactivated vaccine manufacture

Yellow fever (YF) is a high-lethality viral disease, endemic in tropical regions of South America and Africa, with a population of over 900 million people under risk. A highly effective attenuated vaccine, produced in embryonated eggs, has been used for about 80 years. However, egg-based production...

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Bibliographic Details
Published in:Vaccine 2019-05, Vol.37 (24), p.3214-3220
Main Authors: Pato, Tânia P., Souza, Marta C.O., Mattos, Diogo A., Caride, Elena, Ferreira, Davis F., Gaspar, Luciane P., Freire, Marcos S., Castilho, Leda R.
Format: Article
Language:English
Subjects:
Anion exchanging
Bioreactors
Chromatographic techniques
Chromatography
Deactivation
Deoxyribonucleic acid
Disease prevention
DNA
Downstream processing
Eggs
Fever
Gel electrophoresis
Inactivated vaccine
Inactivation
Lethality
Levels
Outbreaks
Production capacity
Proteins
Purification
Recovery
Sodium lauryl sulfate
Tropical environment
Tropical environments
Vaccines
Vector-borne diseases
Vero cells
Viral diseases
Viral envelope proteins
Virus purification
Viruses
Yellow fever virus (YFV)
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Summary:Yellow fever (YF) is a high-lethality viral disease, endemic in tropical regions of South America and Africa, with a population of over 900 million people under risk. A highly effective attenuated vaccine, produced in embryonated eggs, has been used for about 80 years. However, egg-based production limits manufacturing capacity, and vaccine shortage led to the emergency use of a fractional dose (1/5) by the WHO in an outbreak in Africa in 2016 and by Brazilian authorities during an outbreak in 2018. In addition, rare but fatal adverse events of this vaccine have been reported since 2001. These two aspects make clear the need for the development of a new vaccine. In an effort to develop an inactivated YF vaccine, Bio-Manguinhos/FIOCRUZ started developing a new vaccine based on the production of the attenuated 17DD virus in serum-free conditions in Vero cells propagated in bioreactors, followed by chromatography-based purification and β-propiolactone inactivation. Virus purification was studied in this work. Capture was performed using an anion-exchange membrane adsorber (Sartobind® Q), resulting in a virus recovery of 80.2 ± 4.8% and a residual DNA level of 1.3 ± 1.6 ng/dose, thus in accordance with the recommendations of the WHO (
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2019.04.077