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

Abstract

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.

In vivo rescue of arboviruses directly from subgenomic DNA fragments

“…Nevertheless, the main current application of DNA-launched in vivo infection is the development of new strategy to deliver LAV. By combining the ease of preparation, the genetic and thermal stability of traditional DNA vaccines with the high immunogenicity of conventional LAV, DNA-launched LAV could be a strategy for improving the biosafety and distribution of existing LAV [ 23 ]. Several studies have shown that DNA coding for live attenuated viral strains of several arboviruses, such as yellow fever virus and Venezuelan equine encephalitis virus, can induce a protective immune response in mice [ 24–36 ].…”