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Journal of virology2007; 81(24); 13412-13423; doi: 10.1128/JVI.01799-07

Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine.

Abstract: A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly increased humoral responses by several orders of magnitude compared to an equal dose of a conventional DNA vaccine. These increases were also observed at 10- and 100-fold-lower doses of the VEE DNA. Cellular immune responses measured by gamma interferon and interleukin 2 enzyme-linked immunospot assay were significantly higher in mice immunized with the VEE DNA at decreased doses. The immune responses induced by the VEE DNA-encoded antigen, however, were independent of an intact type I interferon signaling pathway. Moreover, the DNA-launched VEE replicon induced an efficient prime to a VEE replicon particle (VRP) boost, increasing humoral and cellular immunity by at least 1 order of magnitude compared to VEE DNA only. Importantly, immunization with VEE DNA, as opposed to VRP, did not induce any anti-VRP neutralizing antibodies. Increased potency of DNA vaccines and reduced vector immunity may ultimately have an impact on the design of vaccination strategies in humans.
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Publication Date: 2007-10-03 PubMed ID: 17913817PubMed Central: PMC2168848DOI: 10.1128/JVI.01799-07Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper presents a new type of genetic vaccine based on a Venezuelan equine encephalitis virus (VEE) replicon, launched from plasmid DNA. The vaccine has demonstrated a higher level of immunogenicity than traditional DNA vaccines, suggesting potential advancements in the field of vaccine development.

About the Research

  • The research provides details about a novel kind of genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon, initiated from plasmid DNA. Plasmids are small, circular, double-stranded DNA molecules that are distinct from a cell’s chromosomal DNA.
  • The involved VEE replicon is encoded under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). Transcription is the first step of gene expression, where a particular segment of DNA is copied into RNA.
  • In vitro studies have confirmed that the VEE DNA could consistently express 3- to 15-fold more green fluorescent protein than a conventional DNA vaccine. In vitro studies are experiments carried out in a controlled environment, such as a petri dish, outside a living organism.

Outcomes

  • Transfection of cells with the VEE replicon induced apoptosis and type I interferon production. Apoptosis is a programmed cell death and type I interferon is a group of proteins that help regulate the activity of the immune system.
  • VEE DNA encoding for human immunodeficiency virus type 1 gp160 significantly increased humoral responses when inoculated into mice, in comparison to an equal dose of a conventional DNA vaccine.
  • The immune response was great, even at 10- and 100-fold-lower doses of the VEE DNA.
  • Higher cellular immune responses, as measured by gamma interferon and interleukin 2 enzyme-linked immunospot assays, were recorded in mice immunized with the VEE DNA at decreased doses. These substances are indicators of how the immune system is reacting.
  • Immunization with VEE DNA, as opposed to VEE replicon particles (VRPs), did not induce any anti-VRP neutralizing antibodies, which shows the potential of this vaccine technology to avoid triggering an unwanted immune response.
  • Overall, the increase in potency of DNA vaccines and the reduced vector immunity suggest a promising avenue for enhancing vaccination techniques in human medicine. Vector immunity is the phenomenon where the immune system attacks the means (vector) through which a vaccine is delivered rather than the antigen it is meant to fight against.

Cite This Article

APA
Ljungberg K, Whitmore AC, Fluet ME, Moran TP, Shabman RS, Collier ML, Kraus AA, Thompson JM, Montefiori DC, Beard C, Johnston RE. (2007). Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine. J Virol, 81(24), 13412-13423. https://doi.org/10.1128/JVI.01799-07

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 81
Issue: 24
Pages: 13412-13423

Researcher Affiliations

Ljungberg, Karl
  • Carolina Vaccine Institute, 9th Floor Burnett-Womack, West Drive, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA. Karl_Ljungberg@med.unc.edu
Whitmore, Alan C
    Fluet, Meagan E
      Moran, Timothy P
        Shabman, Reed S
          Collier, Martha L
            Kraus, Annette A
              Thompson, Joseph M
                Montefiori, David C
                  Beard, Clayton
                    Johnston, Robert E

                      MeSH Terms

                      • Animals
                      • Antibodies, Viral / blood
                      • Apoptosis
                      • Cell Line
                      • Chlorocebus aethiops
                      • Encephalitis Virus, Venezuelan Equine / genetics
                      • Encephalitis Virus, Venezuelan Equine / immunology
                      • Genetic Vectors
                      • HIV Envelope Protein gp160 / genetics
                      • HIV Envelope Protein gp160 / immunology
                      • HIV-1 / genetics
                      • Humans
                      • Immunization
                      • Immunoglobulin G / blood
                      • Interferon Type I / biosynthesis
                      • Interleukin-2 / biosynthesis
                      • L Cells
                      • Mice
                      • Mice, Inbred BALB C
                      • Mice, Knockout
                      • NIH 3T3 Cells
                      • Plasmids / genetics
                      • Promoter Regions, Genetic
                      • Replicon / genetics
                      • Replicon / immunology
                      • Vaccines, DNA / administration & dosage
                      • Vaccines, DNA / genetics
                      • Vaccines, DNA / immunology
                      • Vero Cells

                      Grant Funding

                      • P01 AI050246 / NIAID NIH HHS
                      • P01-AI050246 / NIAID NIH HHS

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