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

Publication ,  Journal Article
Ljungberg, K; Whitmore, AC; Fluet, ME; Moran, TP; Shabman, RS; Collier, ML; Kraus, AA; Thompson, JM; Montefiori, DC; Beard, C; Johnston, RE
Published in: J Virol
December 2007

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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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

December 2007

Volume

81

Issue

24

Start / End Page

13412 / 13423

Location

United States

Related Subject Headings

  • Virology
  • Vero Cells
  • Vaccines, DNA
  • Replicon
  • Promoter Regions, Genetic
  • Plasmids
  • NIH 3T3 Cells
  • Mice, Knockout
  • Mice, Inbred BALB C
  • Mice
 

Citation

APA
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MLA
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Ljungberg, K., Whitmore, A. C., Fluet, M. E., Moran, T. P., Shabman, R. S., Collier, M. L., … Johnston, R. E. (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
Ljungberg, Karl, Alan C. Whitmore, Meagan E. Fluet, Timothy P. Moran, Reed S. Shabman, Martha L. Collier, Annette A. Kraus, et al. “Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine.J Virol 81, no. 24 (December 2007): 13412–23. https://doi.org/10.1128/JVI.01799-07.
Ljungberg K, Whitmore AC, Fluet ME, Moran TP, Shabman RS, Collier ML, et al. Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine. J Virol. 2007 Dec;81(24):13412–23.
Ljungberg, Karl, et al. “Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine.J Virol, vol. 81, no. 24, Dec. 2007, pp. 13412–23. Pubmed, doi:10.1128/JVI.01799-07.
Ljungberg K, Whitmore AC, Fluet ME, Moran TP, Shabman RS, Collier ML, Kraus AA, Thompson JM, Montefiori DC, Beard C, Johnston RE. Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine. J Virol. 2007 Dec;81(24):13412–13423.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

December 2007

Volume

81

Issue

24

Start / End Page

13412 / 13423

Location

United States

Related Subject Headings

  • Virology
  • Vero Cells
  • Vaccines, DNA
  • Replicon
  • Promoter Regions, Genetic
  • Plasmids
  • NIH 3T3 Cells
  • Mice, Knockout
  • Mice, Inbred BALB C
  • Mice