Systematic evaluation of self-adjuvanting lipopeptide nano-vaccine platforms for the induction of potent CD8(+) T-cell responses

Nanomedicine (Lond). 2016 Jan;11(2):137-52. doi: 10.2217/nnm.15.184. Epub 2015 Dec 11.

Abstract

Aim: Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses.

Materials & methods: Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo.

Results: The construct utilizing C12 lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation.

Conclusion: The C12 polylysine platform was an effective configuration for induction of potent CD8(+) T-cell responses.

Keywords: CD8+ T cells; dendritic cells; lipid core peptide; nanovaccine; self-adjuvant; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / chemistry
  • Lauric Acids / chemistry*
  • Lipopeptides / administration & dosage*
  • Lipopeptides / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Particle Size
  • Polylysine / chemistry
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Lauric Acids
  • Lipopeptides
  • Nanocapsules
  • Polylysine
  • 12-aminododecanoic acid