title: DNA-launched live-attenuated vaccines for biodefense applications.
abstract: A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses.
authors.affiliation: a Medigen, Inc ., Frederick , MD , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
authors.affiliation: b Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases , University of Louisville , Louisville , KY , USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.affiliation: c Institute for Human Infections and Immunity, Sealy Center for Vaccine Development and Department of Microbiology and Immunology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: a Medigen, Inc ., Frederick , MD , USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Tretyakova
mesh_terms: D000818:Animals; D006801:Humans; D010957:Plasmids; D012327:RNA Virus Infections / Q000517:prevention & control*; D012328:RNA Viruses / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D012367:RNA, Viral; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: DNA vaccine; Venezuelan equine encephalitis; alphavirus; chikungunya; flavivirus; live-attenuated vaccine; yellow fever