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Development of live-attenuated arenavirus vaccines based on codon deoptimization
Benson Yee Hin Cheng1, Emilio Ortiz-Riaño1, Aitor Nogales1
1Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Journal of Virology
|January 16, 2015
Summary
Developing novel arenavirus vaccines using codon deoptimization shows promise. This approach created attenuated viruses that are safe, stable, and protective against lethal arenavirus challenge.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- Arenaviruses pose significant public health and biodefense threats, causing hemorrhagic fevers.
- No FDA-licensed vaccines currently exist for arenavirus infections.
- Antiviral therapies like ribavirin have limited efficacy and side effects.
Purpose of the Study:
- To explore codon deoptimization (CD) as a novel strategy for developing live-attenuated arenavirus vaccines.
- To generate and evaluate recombinant lymphocytic choriomeningitis virus (LCMV) encoding codon-deoptimized nucleoproteins (NP).
Main Methods:
- Recoded the nucleoprotein (NP) gene of LCMV using mammalian cell-preferred codons.
- Generated recombinant LCMVs (rLCMVs) encoding CD NPs (rLCMV/NP(CD)) via reverse genetics.
- Assessed viral attenuation, genetic stability, and protective efficacy in vitro and in vivo mouse models.
Main Results:
- CD NPs led to reduced NP expression and activity in transfected cells.
- rLCMV/NP(CD) viruses exhibited attenuated growth kinetics in vitro.
- rLCMV/NP(CD1) and rLCMV/NP(CD2) were highly attenuated in vivo but conferred complete protection against lethal WT LCMV challenge after single immunization.
- These vaccine candidates demonstrated genetic and phenotypic stability during serial passages in Vero cells.
Conclusions:
- Codon deoptimization is a viable strategy for creating safe, stable, and effective live-attenuated arenavirus vaccine candidates.
- This approach offers a promising platform for developing vaccines against human-pathogenic arenaviruses.
