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DEC205-DC targeted DNA vaccine against CX3CR1 protects against atherogenesis in mice

Jimmy Jianheng Zhou1,2, Yuan Min Wang1, Vincent W S Lee2,3

  • 1Centre for Kidney Research, Children's Hospital at Westmead, Westmead, NSW, Australia.

Plos One
|April 12, 2018
PubMed

Insights

DNA vaccination targeting the CX3CR1 chemokine receptor reduced atherosclerosis in mice. This approach, which induced high antibody levels without adverse effects, offers a promising therapeutic strategy for atherosclerosis.

Area of Science:

  • Immunology
  • Cardiovascular Research
  • Molecular Medicine

Background:

  • Chemokine CX3CL1 (fractalkine)/CX3CR1 pathway disruption shows promise in reducing atherosclerosis in animal models.
  • Existing methods for pathway interruption lack easy translation to human clinical trials.
  • DNA vaccination presents a potential solution to overcome translational difficulties.

Purpose of the Study:

  • To evaluate the efficacy of a DNA vaccine targeting CX3CR1 in a murine model of atherosclerosis.
  • To investigate the underlying mechanisms of action for CX3CR1 DNA vaccination.
  • To assess the safety and immunogenicity of the targeted DNA vaccine.

Main Methods:

  • DNA vaccination against CX3CR1, enhanced with dendritic cell targeting (DEC-205 scFv), administered to 8-week-old ApoE-/- mice.
  • Mice were fed a normal chow diet.
  • Histological examination of arterial vessels at 34 weeks for atherosclerotic plaque size, macrophage infiltration, smooth muscle cell infiltration, and lipid deposition.

Main Results:

  • High levels of anti-CX3CR1 antibodies were induced, with no apparent adverse reactions.
  • Significantly reduced atherosclerotic plaque in the brachiocephalic artery of vaccinated mice.
  • Reduced macrophage infiltration and lipid deposition in lesions, with no significant change in macrophage phenotype or smooth muscle cell migration.

Conclusions:

  • Targeted DNA vaccination against CX3CR1 is well-tolerated and elicits a robust immune response.
  • This vaccination strategy leads to attenuated atherosclerotic lesions and reduced macrophage infiltration.
  • DNA vaccination targeting chemokine pathways represents a potential therapeutic avenue for atherosclerosis treatment.

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