Zika Virus Attenuation by Codon Pair Deoptimization Induces Sterilizing Immunity in Mouse Models.
Penghui Li1,2, Xianliang Ke1, Ting Wang1,3
1CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
Journal of Virology
|June 22, 2018
Summary
Researchers developed a novel live attenuated Zika virus (ZIKV) vaccine candidate using codon pair deoptimization. The Min E+NS1 variant demonstrated complete protection against lethal ZIKV challenge and vertical transmission in a mouse model.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- Zika virus (ZIKV) epidemics in the Americas caused severe congenital abnormalities and fetal demise.
- No effective vaccines or antiviral treatments are currently available for ZIKV infection.
Purpose of the Study:
- To design and evaluate novel live attenuated ZIKV vaccine candidates using codon pair deoptimization.
- To assess the safety and efficacy of these candidates in preventing ZIKV infection and transmission.
Main Methods:
- Synthesized three codon pair-deoptimized ZIKV variants (Min E, Min NS1, Min E+NS1) using reverse genetics.
- Assessed replication fitness in Vero and insect cells, and virulence in a mouse model.
- Evaluated immunogenicity and protective efficacy against lethal ZIKV challenge and vertical transmission.
Main Results:
- Codon pair-deoptimized ZIKVs showed reduced replication in mammalian cells and enhanced replication in insect cells.
- The Min E+NS1 variant exhibited diminished virulence and induced sterilizing immunity with high neutralizing antibody titers.
- A single immunization with Min E+NS1 provided complete protection against lethal challenge and vertical transmission in pregnant mice.
Conclusions:
- Codon pair deoptimization is a feasible strategy for developing safe and effective live attenuated ZIKV vaccines.
- The Min E+NS1 variant shows significant potential as a vaccine candidate to prevent ZIKV infection and its devastating consequences.
- The synonymous mutational approach minimizes the risk of reversion to wild-type virulence, enhancing vaccine safety.
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