Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA

Drug Deliv. 2016 Sep;23(7):2596-2607. doi: 10.3109/10717544.2015.1038856. Epub 2015 May 29.

Abstract

In recent years, mRNA-based vaccines have emerged to be a great alternative to DNA-based vaccines due to the safety of not inserting into host genome. However, mRNA molecules are single-stranded nucleic acids that are vulnerable under RNase existing in human skin and tissues. In this study, a self-assembled cationic nanomicelles based on polyethyleneimine-stearic acid (PSA) copolymer were developed to delivery HIV-1 gag encoding mRNA to dendritic cells and BALB/c mice. We evaluated the transfection efficiency and cell uptake efficiency of naked EGFP mRNA, PSA, PEI-2k and PEI-25k nanoparticles format on DC2.4 cell lines. Immune responses after sub-cutaneous administration of gag mRNA to BALB/c mice were notably induced by PSA as compared with naked gag mRNA. We found the PSA/mRNA nanomicelles were potent systems that can effectively deliver mRNA and induce antigen-specific immune response, stimulating various new vaccine strategies using mRNA.

Keywords: Cationic polymers; HIV-1 gag; endosome escape; intracellular cytokine staining; messenger RNA.

MeSH terms

  • Animals
  • Cations / chemistry*
  • Dendritic Cells / chemistry*
  • Genes, gag / drug effects*
  • Genes, gag / genetics
  • Genes, gag / immunology
  • HIV-1 / chemistry
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • Ribonucleases / chemistry
  • Ribonucleases / immunology*
  • Ribonucleases / metabolism
  • Stearic Acids / chemistry
  • Transfection
  • Vaccines / chemistry
  • Vaccines / immunology*
  • Vaccines / metabolism

Substances

  • Cations
  • Micelles
  • RNA, Messenger
  • Stearic Acids
  • Vaccines
  • polyethyleneimine-stearic acid
  • Ribonucleases