Novel vaccine against Venezuelan equine encephalitis combines advantages of DNA immunization and a live attenuated vaccine

Abstract

DNA vaccines combine remarkable genetic and chemical stability with proven safety and efficacy in animal models, while remaining less immunogenic in humans. In contrast, live-attenuated vaccines have the advantage of inducing rapid, robust, long-term immunity after a single-dose vaccination. Here we describe novel iDNA vaccine technology that is based on an infectious DNA platform and combines advantages of DNA and live attenuated vaccines. We applied this technology for vaccination against infection with Venezuelan equine encephalitis virus (VEEV), an alphavirus from the Togaviridae family. The iDNA vaccine is based on transcription of the full-length genomic RNA of the TC-83 live-attenuated virus from plasmid DNA in vivo. The in vivo-generated viral RNA initiates limited replication of the vaccine virus, which in turn leads to efficient immunization. This technology allows the plasmid DNA to launch a live-attenuated vaccine in vitro or in vivo. Less than 10 ng of pTC83 iDNA encoding the full-length genomic RNA of the TC-83 vaccine strain initiated replication of the vaccine virus in vitro. In order to evaluate this approach in vivo, BALB/c mice were vaccinated with a single dose of pTC83 iDNA. After vaccination, all mice seroconverted with no adverse reactions. Four weeks after immunization, animals were challenged with the lethal epidemic strain of VEEV. All iDNA-vaccinated mice were protected from fatal disease, while all unvaccinated controls succumbed to infection and died. To our knowledge, this is the first example of launching a clinical live-attenuated vaccine from recombinant plasmid DNA in vivo.

Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles

“…At different time intervals (0, 6,12,18,24,36,48,72,96,120,144,168,192,216, and 240 hours), a sample was taken and centrifuged at 10,000 r/min for 10 minutes at 4°C. The concentration of released plasmid DNA in the supernatant was determined using UV spectrophotometry.…”

“…5,6 A major problem with the use of inactivated vaccines administered by the mucosal route is that they generally have poor immunogenicity and can cause disease if they are not completely inactivated. 7 Due to the disadvantages of these vaccines, there is a need to improve and extend the impact of vaccination programs against NDV.…”

Mouse models of alphavirus-induced inflammatory disease

“…A diverse range of vaccination strategies has been investigated along with a variety of vaccine candidates including replicons and adenovirusand DNA-based vaccines (Schäfer et al, 2009;Tretyakova et al, 2013;Williams et al, 2009). Studies have examined the immunological profile of BALB/c mice following vaccination with live attenuated VEEV strain (TC-83) given at 10 5 p.f.u.…”

Newcastle disease virus vaccine encapsulated in biodegradable nanoparticles for mucosal delivery of a human vaccine

“…Live vaccines can be administrated by feeding, drinking, aerosol and spray. However, a major problem of live vaccine is the requirements for both biocontainment and cold chain, 11,12 especially potential damage due to partial virus toxicity reservation. 13 Inactivated vaccines could not elicit an efficient antibody response after the single immunization.…”