Generation of influenza A viruses as live but replication-incompetent virus vaccines

The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated pr...

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Published inScience (American Association for the Advancement of Science) Vol. 354; no. 6316; pp. 1170 - 1173
Main Authors Si, Longlong, Xu, Huan, Zhou, Xueying, Zhang, Ziwei, Tian, Zhenyu, Wang, Yan, Wu, Yiming, Zhang, Bo, Niu, Zhenlan, Zhang, Chuanling, Fu, Ge, Xiao, Sulong, Xia, Quig, Zhang, Lihe, Zhou, Demin
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 02.12.2016
The American Association for the Advancement of Science
Subjects
Aluminum
Animals
Biotechnology
Codon, Nonsense
Ferrets
Genetic code
Genome, Viral
Genomics
Guinea Pigs
HEK293 Cells
Humans
Immunogenicity, Vaccine
Influenza
Influenza A virus
Influenza A virus - genetics
Influenza A virus - immunology
Influenza A virus - physiology
Influenza Vaccines - genetics
Influenza Vaccines - immunology
Methanosarcina barkeri - genetics
Mice
Models, Animal
Mustela
Orthomyxoviridae
Protein Biosynthesis - genetics
T-Lymphocytes - immunology
Transgenes
Transgenic
Vaccination
Vaccines
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Viral Plaque Assay
Virus Cultivation - methods
Virus Replication - genetics
Viruses
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Abstract The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infect i vi ty but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
AbstractList The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infect i vi ty but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
Protecting by changing the codeLive attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an attempt to get around this, Si et al. expanded the genetic code of influenza A viruses. They propagated viruses that were mutated to encode premature termination codons (PTCs) in a cell line engineered to be able to express these flu proteins. Despite not being able to replicate in conventional cells, PTC-containing viruses were highly immunogenic and protected mice, guinea pigs, and ferrets against influenza challenge.Science, this issue p. 1170 The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
Genetic code expansion and orthogonal translation machinery are used to generate live, attenuated viral vaccines. Live attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an attempt to get around this, Si et al. expanded the genetic code of influenza A viruses. They propagated viruses that were mutated to encode premature termination codons (PTCs) in a cell line engineered to be able to express these flu proteins. Despite not being able to replicate in conventional cells, PTC-containing viruses were highly immunogenic and protected mice, guinea pigs, and ferrets against influenza challenge. Science , this issue p. 1170 The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)–harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell–mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
Live attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an attempt to get around this, Si et al. expanded the genetic code of influenza A viruses. They propagated viruses that were mutated to encode premature termination codons (PTCs) in a cell line engineered to be able to express these flu proteins. Despite not being able to replicate in conventional cells, PTC-containing viruses were highly immunogenic and protected mice, guinea pigs, and ferrets against influenza challenge. Science, this issue p. 1170 The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
Author Tian, Zhenyu
Zhou, Demin
Wu, Yiming
Niu, Zhenlan
Zhang, Ziwei
Zhang, Chuanling
Xiao, Sulong
Wang, Yan
Xu, Huan
Zhang, Lihe
Si, Longlong
Zhang, Bo
Zhou, Xueying
Fu, Ge
Xia, Quig
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  surname: Zhang
  fullname: Zhang, Ziwei
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  givenname: Zhenyu
  surname: Tian
  fullname: Tian, Zhenyu
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  givenname: Yan
  surname: Wang
  fullname: Wang, Yan
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  surname: Wu
  fullname: Wu, Yiming
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  givenname: Lihe
  surname: Zhang
  fullname: Zhang, Lihe
– sequence: 15
  givenname: Demin
  surname: Zhou
  fullname: Zhou, Demin
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27934767$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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Snippet The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded...
Genetic code expansion and orthogonal translation machinery are used to generate live, attenuated viral vaccines. Live attenuated vaccines can be very potent,...
Live attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an attempt to get around this, Si et...
Protecting by changing the codeLive attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an...
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SubjectTerms Aluminum
Animals
Biotechnology
Codon, Nonsense
Ferrets
Genetic code
Genome, Viral
Genomics
Guinea Pigs
HEK293 Cells
Humans
Immunogenicity, Vaccine
Influenza
Influenza A virus
Influenza A virus - genetics
Influenza A virus - immunology
Influenza A virus - physiology
Influenza Vaccines - genetics
Influenza Vaccines - immunology
Methanosarcina barkeri - genetics
Mice
Models, Animal
Mustela
Orthomyxoviridae
Protein Biosynthesis - genetics
T-Lymphocytes - immunology
Transgenes
Transgenic
Vaccination
Vaccines
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Viral Plaque Assay
Virus Cultivation - methods
Virus Replication - genetics
Viruses
Title Generation of influenza A viruses as live but replication-incompetent virus vaccines
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