ZIKV can be effectively attenuated by codon pair deoptimization
From June 2015, unprecedented epidemics of Zika virus (ZIKV) occur in the Americas, which cause the unexpected clinical symptoms including Guillain-Barre？ syndrome, microcephaly and other birth defects in human.
To date, there is no effective licensed vaccine or antiviral treatment against ZIKV infection, although several vaccine candidates have been described including formalin inactivated vaccines, live attenuated vaccines, genetic vaccines, and virus-like particle (VLP) vaccines. Therefore, new options for the development of ZIKV vaccine are needed.
In a recent report, the research group led by Prof. WANG Hanzhong in Wuhan Institute of Virology of the Chinese Academy of Sciences provided the first attenuated versions of ZIKV with two important genes (E and/or NS1) that were subjected to codon pair deoptimization. Compared to parental ZIKV, the codon pair-deoptimized ZIKVs were mammalian-attenuated, and preferred insect to mammalian Cells. Min E+NS1, the most restrictive variant, induced sterilizing immunity with a robust neutralizing antibody titer, and achieved complete protection against lethal challenge and vertical virus transmission during pregnancy.
In this study, the scientists describe the first large-scale recoding of ZIKV, a flavivirus that belongs to a large family of mosquito-borne human pathogens. Min E+NS1 displayed the potential to develop into a promising live-attenuated vaccine candidate.
Results from this study demonstrated the feasibility of rapid attenuation of ZIKV through the codon pair deoptimization strategy. The unparalleled advantage of the codon pair deoptimization strategy is that reversion to wild-type virulence is unlikely due to numerous synonymous substitutions without changing the amino acid sequence.
In summary, the codon pair deoptimization strategy would add the safety to the features of live attenuated viruses, which has a broad application in the development of vaccines for flavivirus and other important viruses.
The results have been published in Journal of Virology entitled "Zika Virus Attenuation by Codon Pair Deoptimization Induces Sterilizing Immunity in Mouse Models".
This work was supported by the National Key R&D Program of China, the National Natural Science Foundation of China (NSFC) and Youth Innovation Promotion Association of CAS.
Immunohistochemical staining of E protein in brain sections from infected mice. Image by WANG Hanzhong
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China (http://english.whiov.cas.cn/)