Attenuation of Tick-Borne Encephalitis Virus Using Large-Scale Random Codon Re-encoding


The arbovirus Tick-borne encephalitis virus (TBEV; genus Flavivirus) is transmitted by ticks of the Ixodes genus. TBEV causes febrile illness and encephalitis in humans in forested regions of Europe and Asia. The incidence of TBE is increasing across Central and Eastern European countries despite the availability of several licensed inactivated vaccines and appropriate vaccination programmes. Large-scale codon re-encoding, a recently developed attenuation method that modifies viral RNA nucleotide composition of large coding regions without alteration of the encoded proteins, has been successfully applied to a variety of RNA viruses. In contrast with previous empirical methods of generating live attenuated vaccines, large-scale codon re-encoding facilitates rapid generation of vaccine candidates using reverse genetics methods, by direct control of the attenuation phenotype. Additional benefits include reduced costs and induction of long-term immunity. Here, we have applied the large-scale codon re-encoding method to the TBEV to demonstrate the principle of developing a live attenuated virus vaccine which protects mice against subsequent infection with the wild type virulent virus. This study therefore illustrates that codon re-encoding is potentially an easily derived and effective method of producing live attenuated vaccine candidates against positive-stranded RNA viruses.


Vyšlo v časopise: Attenuation of Tick-Borne Encephalitis Virus Using Large-Scale Random Codon Re-encoding. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004738
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004738

Souhrn

The arbovirus Tick-borne encephalitis virus (TBEV; genus Flavivirus) is transmitted by ticks of the Ixodes genus. TBEV causes febrile illness and encephalitis in humans in forested regions of Europe and Asia. The incidence of TBE is increasing across Central and Eastern European countries despite the availability of several licensed inactivated vaccines and appropriate vaccination programmes. Large-scale codon re-encoding, a recently developed attenuation method that modifies viral RNA nucleotide composition of large coding regions without alteration of the encoded proteins, has been successfully applied to a variety of RNA viruses. In contrast with previous empirical methods of generating live attenuated vaccines, large-scale codon re-encoding facilitates rapid generation of vaccine candidates using reverse genetics methods, by direct control of the attenuation phenotype. Additional benefits include reduced costs and induction of long-term immunity. Here, we have applied the large-scale codon re-encoding method to the TBEV to demonstrate the principle of developing a live attenuated virus vaccine which protects mice against subsequent infection with the wild type virulent virus. This study therefore illustrates that codon re-encoding is potentially an easily derived and effective method of producing live attenuated vaccine candidates against positive-stranded RNA viruses.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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