Experimental DNA-Launched Live-Attenuated Vaccines Against Infections Caused by Flavi- and Alphaviruses

Pushko, Peter; Bredenbeek, Peter J.; Lukashevich, Igor S.

doi:10.1007/978-3-7091-1818-4_6

Cited by 3 publications

(6 citation statements)

References 58 publications

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“…1). This platform represents recombinant DNA that can launch live-attenuated virus in vitro or in vivo [19-25]. DNA-launched live-attenuated vaccines were sometimes called iDNA® vaccines to distinguish them from traditional DNA vaccines [19-21].…”

Section: Dna-launched Live-attenuated Vaccines As Novel Dna Vaccinesmentioning

confidence: 99%

“…1). Essentially, the iDNA plasmid turns a limited number of cells in the vaccine recipient into the cell-scale factories for “manufacturing” of live-attenuated vaccine [19, 20, 25]. …”

Section: Dna-launched Live-attenuated Vaccines As Novel Dna Vaccinesmentioning

confidence: 99%

“…This platform minimizes the potential for reversions or adverse effects of traditional live-attenuated vaccine, ensures genetic stability, and results in efficient immunization in animal models [19-21, 25, 32]. The technology involves many advantages of a DNA immunization and live-attenuated vaccines and potentially, can enhance not only safety but also immunogenicity and efficacy of live-attenuated vaccine.…”

Section: Expert Commentarymentioning

confidence: 99%

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DNA-launched live-attenuated vaccines for biodefense applications

Pushko

Lukashevich

Weaver

et al. 2016

Expert Review of Vaccines

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Summary 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.

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Section: Dna-launched Live-attenuated Vaccines As Novel Dna Vaccinesmentioning

confidence: 99%

“…1). Essentially, the iDNA plasmid turns a limited number of cells in the vaccine recipient into the cell-scale factories for “manufacturing” of live-attenuated vaccine [19, 20, 25]. …”

Section: Dna-launched Live-attenuated Vaccines As Novel Dna Vaccinesmentioning

confidence: 99%

Section: Expert Commentarymentioning

confidence: 99%

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DNA-launched live-attenuated vaccines for biodefense applications

Pushko

Lukashevich

Weaver

et al. 2016

Expert Review of Vaccines

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“…The technology utilizes recombinant plasmid DNA encoding an entire genome of a live-attenuated virus. The iDNA plasmids can launch live-attenuated viruses in vitro for live-attenuated vaccine manufacturing, or directly in vivo for effective DNA vaccination [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. These DNA vaccines represent a novel nucleic acid vaccine technology that combines the chemical and genetic stability of DNA with the exceptional efficacy of live-attenuated vaccines ( Figure 1 A).…”

Section: Introduction: Advantages Of Idna As Dna Vaccinesmentioning

confidence: 99%

Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses

Pushko,

Lukashevich,

Johnson

et al. 2024

Viruses

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Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in vivo. When iDNA is injected into mammalian cells in vitro or in vivo, the RNA genome of an attenuated virus is transcribed, which starts replication of a defined, live-attenuated vaccine virus in cell culture or the cells of a vaccine recipient. In the latter case, an immune response to the live virus vaccine is elicited, which protects against the pathogenic virus. Unlike other nucleic acid vaccines, such as mRNA and standard DNA vaccines, iDNA vaccines elicit protection with a single dose, thus providing major improvement to epidemic preparedness. Still, iDNA vaccines retain the advantages of other nucleic acid vaccines. In summary, the iDNA platform combines the advantages of reverse genetics and DNA immunization with the high immunogenicity of live-attenuated vaccines, resulting in enhanced safety and immunogenicity. This vaccine platform has expanded the field of genetic DNA and RNA vaccines with a novel type of immunogenic DNA vaccines that encode entire live-attenuated viruses.

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“…This platform is based on the infectious clone technology and represents plasmid DNA that encodes the full-length virus RNA and can initiate replication of viral RNA and launch live-attenuated virus in vitro or in vivo (Jiang et al, 2015; Pushko et al, 2014; Tretyakova et al, 2014a; Tretyakova et al, 2014b). DNA-launched live-attenuated vaccines were sometimes called iDNA® vaccines in order to distinguish them from the standard DNA vaccines (Pushko et al, 2016; Tretyakova et al, 2013; Tretyakova et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

Plasmid DNA launches live-attenuated Japanese encephalitis virus and elicits virus-neutralizing antibodies in BALB/c mice

et al. 2017

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We describe novel plasmid DNA that encodes the full-length Japanese encephalitis virus (JEV) genomic cDNA and launches live-attenuated JEV vaccine in vitro and in vivo. The synthetic cDNA based on the sequence of JEV SA14-14-2 live-attenuated virus was placed under transcriptional control of the cytomegalovirus major immediate-early promoter. The stability and yields of the plasmid in E. coli were optimized by inserting three synthetic introns that disrupted JEV cDNA in the structural and nonstructural genes. Transfection of Vero cells with the resulting plasmid resulted in the replication of JEV vaccine virus with intron sequences removed from viral RNA. Furthermore, a single-dose vaccination of BALB/c mice with 0.5 – 5 μg of plasmid resulted in successful seroconversion and elicitation of JEV virus-neutralizing serum antibodies. The results demonstrate the possibility of using DNA vaccination to launch live-attenuated JEV vaccine and support further development of DNA-launched live-attenuated vaccine for prevention of JEV infections.

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Experimental DNA-Launched Live-Attenuated Vaccines Against Infections Caused by Flavi- and Alphaviruses

Cited by 3 publications

References 58 publications

DNA-launched live-attenuated vaccines for biodefense applications

DNA-launched live-attenuated vaccines for biodefense applications

Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses

Plasmid DNA launches live-attenuated Japanese encephalitis virus and elicits virus-neutralizing antibodies in BALB/c mice

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