Loading dendritic cells with gold nanoparticles (GNPs) bearing HIV-peptides and mannosides enhance HIV-specific T cell responses

Nanomedicine. 2018 Feb;14(2):339-351. doi: 10.1016/j.nano.2017.11.009. Epub 2017 Nov 20.

Abstract

Gold nanoparticles (GNPs) decorated with glycans ameliorate dendritic cells (DC) uptake, antigen-presentation and T-cells cross-talk, which are important aspects in vaccine design. GNPs allow for high antigen loading, DC targeting, lack of toxicity and are straightforward prepared and easy to handle. The present study aimed to assess the capacity of DC to process and present HIV-1-peptides loaded onto GNPs bearing high-mannoside-type oligosaccharides (P1@HM) to autologous T-cells from HIV-1 patients. The results showed that P1@HM increased HIV-specific CD4+ and CD8+ T-cell proliferation and induced highly functional cytokine secretion compared with HIV-peptides alone. P1@HM elicits a highly efficient secretion of pro-TH1 cytokines and chemokines, a moderate production of pro-TH2 and significant higher secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. Thus, co-delivery of HIV-1 antigens and HM by GNPs is an excellent vaccine delivery system inducing HIV-specific cellular immune responses in HIV+ patients, being a promising approach to improve anti-HIV-1 vaccines.

Keywords: CMV; Cellular immunity; Gold nanoparticles (GNPs); HIV-1; High-mannoside-type oligosaccharides; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cells, Cultured
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Gold / chemistry*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation
  • Mannosides / chemistry
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Phosphoproteins / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Matrix Proteins / immunology
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Chemokines
  • Cytokines
  • Mannosides
  • Peptide Fragments
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • gag Gene Products, Human Immunodeficiency Virus
  • Gold