Self-assembling peptide for co-delivery of HIV-1 CD8+ T cells epitope and Toll-like receptor 7/8 agonists R848 to induce maturation of monocyte derived dendritic cell and augment polyfunctional cytotoxic T lymphocyte (CTL) response

J Control Release. 2016 Aug 28:236:22-30. doi: 10.1016/j.jconrel.2016.06.019. Epub 2016 Jun 11.

Abstract

Peptide based vaccine that incorporates one or several highly conserved CD8+ T cells epitopes to induce potent cytotoxic T lymphocyte (CTL) response is desirable for some infectious diseases, such as HIV-1 (human immunodeficiency virus-1), and cancers. However, the CD8+ T cells epitope is often weakly immunogenic, and thus requires a specific adjuvant or delivery system to enhance the efficiency. Here we investigated the use of self-assembling peptide EAK16-II based platform to achieve the co-delivery of CD8+ T cells epitope and TLR7/8 agonists (R848 or R837) for augmenting DCs maturation and HIV-1 specific CTL response. HIV-1 CTL epitope SL9 was conjugated with EAK16-II to obtain SL9-EAK16-II, which further spontaneously co-assembled with R848 or R837 in aqueous solution, forming co-assembled nanofibers. Fluorescence spectra and calorimetrical titration revealed the interaction between SL9-EAK16-II assemblies and R848 or R837 via hydrogen bonding and hydrophobic interaction, with the binding affinity (dissociation constant Kd) of 0.62μM or 0.53μM, respectively. Ex vivo generated DCs from HIV-1+ patients pulsed with the SL9-EAK16-II/R848 nanofibers stimulated significantly more polyfunctional SL9 specific CTLs, compared to the DCs pulsed with SL9 alone or the mixture of SL9 and TLR agonist. Furthermore, the nanofibers elicited stronger SL9 specific CTL response in vaccinated mice. Our findings suggest the self-assembling peptide EAK16-II might be used as a new delivery system for peptide based vaccines.

Keywords: Co-assembly; Co-delivery; Peptide; Vaccine.

MeSH terms

  • Animals
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Delivery Systems
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Female
  • HIV-1 / immunology*
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Imidazoles / administration & dosage*
  • Membrane Glycoproteins / agonists*
  • Membrane Glycoproteins / metabolism
  • Mice, Transgenic
  • Monocytes / immunology
  • Monocytes / metabolism
  • Nanofibers / chemistry*
  • Particle Size
  • Quinolines / administration & dosage
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / agonists*
  • Toll-Like Receptor 8 / metabolism
  • Vaccination

Substances

  • 1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amine
  • Epitopes, T-Lymphocyte
  • Imidazoles
  • Membrane Glycoproteins
  • Quinolines
  • TLR8 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • resiquimod