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Attenuation of tick-borne encephalitis virus using large-scale random codon re-encoding.

Lauriane de Fabritus1, Antoine Nougairède2, Fabien Aubry1

  • 1Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 "Emergence des Pathologies Virales", Marseille, France.

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|March 4, 2015
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Summary

Large-scale codon re-encoding created an attenuated tick-borne encephalitis virus (TBEV). This re-encoded TBEV protected mice against virulent wild-type virus, showing potential as a live-attenuated vaccine candidate.

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Area of Science:

  • Virology
  • Vaccinology
  • Molecular Biology

Background:

  • Tick-borne encephalitis virus (TBEV) is a pathogenic flavivirus causing severe human illness in Europe and Asia.
  • Attenuated viruses are crucial for developing live-attenuated vaccines.
  • Codon re-encoding is an emerging strategy for viral attenuation.

Purpose of the Study:

  • To investigate the efficacy of large-scale codon re-encoding in attenuating TBEV.
  • To evaluate the immunogenicity and protective potential of the re-encoded TBEV in a mouse model.

Main Methods:

  • Synonymous mutations were introduced into the NS5 coding region of a TBEV infectious clone.
  • The re-encoded virus was characterized for in vitro replication and in vivo pathogenicity in mice.
  • Mice were inoculated with re-encoded TBEV, and subsequent challenge with wild-type TBEV was performed.

Main Results:

  • Re-encoding resulted in a slightly reduced in vitro replication fitness.
  • The re-encoded TBEV exhibited significantly decreased viraemia, neurovirulence, and neuroinvasiveness in mice.
  • Mice infected with re-encoded TBEV developed neutralizing antibodies and were protected against wild-type TBEV challenge.

Conclusions:

  • Random codon re-encoding is a viable method for generating attenuated flaviviruses.
  • Re-encoded TBEV demonstrates potential as a safe and effective live-attenuated vaccine candidate.
  • This approach offers a promising strategy for controlling TBEV and other pathogenic flaviviruses.