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The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors.

Publication ,  Journal Article
Wloch, MK; Pasquini, S; Ertl, HC; Pisetsky, DS
Published in: Hum Gene Ther
July 1, 1998

To determine the influence of DNA sequence on immunostimulatory properties of vaccine vectors, we tested the induction of in vitro and in vivo immune responses by plasmids modified to contain extended runs of dG sequences. Studies with oligonucleotides indicate that dG sequences can directly stimulate B cells as well as enhance the activity of immunostimulatory CpG motifs because of interaction with the macrophage scavenger receptor (MSR); this receptor can bind a variety of polyanions including dG sequences. To modify vectors, we introduced stretches of 20-60 dG residues into the pCMV-beta and pSG5rab.gp vectors and measured the ability of these plasmids to induce IL-12 and IFN-gamma production by murine splenocytes. The induction of in vivo antibody responses to rabies glycoprotein was also assessed with the pSG5rab.gp vectors. In in vitro cultures, cytokine production induced by plasmids with and without dG sequences was similar. Furthermore, the addition of dG sequences to pSG5rab.gp vectors failed to enhance the anti-rabies glycoprotein response to immunization. To assess further mechanisms by which plasmids stimulate macrophages, we measured the effects of MSR ligands on in vitro cytokine induction. In in vitro cultures, poly(G), dG30, and fucoidan inhibited IL-12 induction by plasmids. IL-12 induction was also inhibited by mammalian DNA but was unaffected by polyanions that are not MSR ligands. Together, these results suggest that the addition of 20 to 60-base dG sequences to plasmids does not significantly affect their properties as immunostimulators or vaccines. Furthermore, these results suggest that MSR ligands can block cytokine induction by plasmid DNA whether or not the plasmid contains extended runs of dG.

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Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

July 1, 1998

Volume

9

Issue

10

Start / End Page

1439 / 1447

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Receptors, Scavenger
  • Receptors, Immunologic
  • Oligonucleotides
  • Mice, Inbred C3H
  • Mice
  • Ligands
  • Interleukin-12
  • Interferon-gamma
  • Guanine
 

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Wloch, M. K., Pasquini, S., Ertl, H. C., & Pisetsky, D. S. (1998). The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors. Hum Gene Ther, 9(10), 1439–1447. https://doi.org/10.1089/hum.1998.9.10-1439
Wloch, M. K., S. Pasquini, H. C. Ertl, and D. S. Pisetsky. “The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors.Hum Gene Ther 9, no. 10 (July 1, 1998): 1439–47. https://doi.org/10.1089/hum.1998.9.10-1439.
Wloch MK, Pasquini S, Ertl HC, Pisetsky DS. The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors. Hum Gene Ther. 1998 Jul 1;9(10):1439–47.
Wloch, M. K., et al. “The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors.Hum Gene Ther, vol. 9, no. 10, July 1998, pp. 1439–47. Pubmed, doi:10.1089/hum.1998.9.10-1439.
Wloch MK, Pasquini S, Ertl HC, Pisetsky DS. The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors. Hum Gene Ther. 1998 Jul 1;9(10):1439–1447.
Journal cover image

Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

July 1, 1998

Volume

9

Issue

10

Start / End Page

1439 / 1447

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Receptors, Scavenger
  • Receptors, Immunologic
  • Oligonucleotides
  • Mice, Inbred C3H
  • Mice
  • Ligands
  • Interleukin-12
  • Interferon-gamma
  • Guanine