Chinese scientists have reported a new strategy for developing live virus vaccines
Source：Longlong Si
2016-12-05
The research team of Prof. Demin Zhou/Academician Lihe Zhang at Peking University demonstrated the newstrategy for generation of live influenza A virus vaccine. This finding is published by Scienceas entitled “Generation of influenza A virusesas live but replication-incompetentvirus vaccines”on December 2, 2016.
The greatest challenge for converting viruses, such as those responsible for influenza, Ebola, and AIDS pandemics, into live whole-virion vaccines is to render them as avirulent as possible while maintaining their full infectivity to elicit sufficient immunity. Themodern technology of genetic code expansionand its application to the viral genome may provide the potential to generate livebut replication-incompetent virus vaccines eliciting strong and broad immunity.
In this study, Prof. Zhou’s team used the genetic codon expansion technology as a switch to control the replication of influenza virus, thus reverse dangerous wild-type virus into safe vaccine. They introduced amber stop codon into the viral genome, leading to the generation of premature termination codon(PTC)-harbouring virus. The PTC viruscould only replicate in a stable cell line that stably express orthogonal tRNA/pylRS pair in the presence of artificially synthesized unnatural amino acid, but not in normal environment that lacking the orthogonal translation system. By this way, the PTC virus could be used as vaccine. And by optimizing the sites and number of amber codon introduced in viral genome, theresultant viruses could be the prophylactic or therapeutic vaccines.
In theory, generation ofsuch PTC virus vaccines can be potentially adaptedto almost any virus so long as their genomecould be manipulated and packaged in a cell line. Therefore, the new strategy reported by Prof. Demin Zhou may represent a potential revolution in virus vaccinology.
Professor Demin Zhou and Academician Lihe Zhang are from State Key Laboratory of Natural and Niomimatic Drugs, School of Pharmaceutical Sciences, Peking University. Doctoral students Longlong Si and Huan Xu are the co-first authors of the Science paper.
Si L., Xu H., Zhou X., Zhang Z., Tian Z., Wang Y., Wu Y., Zhang B., Niu Z., Zhang C., Fu G., Xiao S., Xia Q., Zhang L., and Zhou D*. Science, 2016, 354(6316), 1170-1173.
The greatest challenge for converting viruses, such as those responsible for influenza, Ebola, and AIDS pandemics, into live whole-virion vaccines is to render them as avirulent as possible while maintaining their full infectivity to elicit sufficient immunity. Themodern technology of genetic code expansionand its application to the viral genome may provide the potential to generate livebut replication-incompetent virus vaccines eliciting strong and broad immunity.
In this study, Prof. Zhou’s team used the genetic codon expansion technology as a switch to control the replication of influenza virus, thus reverse dangerous wild-type virus into safe vaccine. They introduced amber stop codon into the viral genome, leading to the generation of premature termination codon(PTC)-harbouring virus. The PTC viruscould only replicate in a stable cell line that stably express orthogonal tRNA/pylRS pair in the presence of artificially synthesized unnatural amino acid, but not in normal environment that lacking the orthogonal translation system. By this way, the PTC virus could be used as vaccine. And by optimizing the sites and number of amber codon introduced in viral genome, theresultant viruses could be the prophylactic or therapeutic vaccines.
In theory, generation ofsuch PTC virus vaccines can be potentially adaptedto almost any virus so long as their genomecould be manipulated and packaged in a cell line. Therefore, the new strategy reported by Prof. Demin Zhou may represent a potential revolution in virus vaccinology.
Professor Demin Zhou and Academician Lihe Zhang are from State Key Laboratory of Natural and Niomimatic Drugs, School of Pharmaceutical Sciences, Peking University. Doctoral students Longlong Si and Huan Xu are the co-first authors of the Science paper.
Si L., Xu H., Zhou X., Zhang Z., Tian Z., Wang Y., Wu Y., Zhang B., Niu Z., Zhang C., Fu G., Xiao S., Xia Q., Zhang L., and Zhou D*. Science, 2016, 354(6316), 1170-1173.
