PEGylated cationic liposomes robustly augment vaccine-induced immune responses: Role of lymphatic trafficking and biodistribution

J Control Release. 2012 Apr 10;159(1):135-42. doi: 10.1016/j.jconrel.2011.12.017. Epub 2011 Dec 29.

Abstract

Lymph nodes (LNs) are peripheral lymphoid organs essential for vaccine-induced immune responses. Although cationic liposomes have been documented as a novel adjuvant and vaccine delivery system, whether enhancing LN targeting would improve the efficiency of cationic liposome-formulated vaccines has not been elucidated yet. In the present study we investigated the effect of PEGylation on LN targeting and the immunogenicity of cationic liposome-formulated vaccines. DOTAP cationic liposomes were incorporated with 1 or 5mol% of DSPE-PEG2000 and labeled with near infrared fluorescent dyes. The lymphatic trafficking and biodistribution of different liposomes after subcutaneous (s.c.) injection were recorded using an in-vivo imaging system. The results showed that incorporation of 1mol% DSPE-PEG2000 not only accelerated the drainage of DOTAP liposomes into draining LNs, but also prolonged their LN retention and enhanced liposome uptake by resident antigen-presenting cells. On the other hand, although incorporating 5mol% of DSPE-PEG2000 into DOTAP liposomes enhanced their LN retention and uptake to a lesser extent, it prolonged blood circulation of DOTAP liposomes and increased their splenic accumulation. In addition, PEGylated DOTAP liposomes augmented primary and secondary anti-OVA antibody responses more potently than nonPEGylated DOTAP liposomes did. Hence, incorporating a small amount of DSPE-PEG2000 into DOTAP liposomes not only increased the passive LN targeting of DOTAP-formulated vaccines but also modulated their biodistribution in vivo, which consequently improved the efficiency of cationic liposome-formulated vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens / administration & dosage
  • Antigens / chemistry
  • Antigens / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Acids, Monounsaturated / chemistry*
  • Female
  • Immunoglobulin G / blood
  • Liposomes / administration & dosage
  • Liposomes / chemistry*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin / administration & dosage
  • Ovalbumin / chemistry
  • Ovalbumin / immunology
  • Phosphatidylethanolamines / administration & dosage
  • Phosphatidylethanolamines / chemistry*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry*
  • Quaternary Ammonium Compounds / administration & dosage
  • Quaternary Ammonium Compounds / chemistry*
  • Tissue Distribution
  • Vaccination
  • Vaccines / administration & dosage
  • Vaccines / chemistry
  • Vaccines / immunology

Substances

  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • Adjuvants, Immunologic
  • Antigens
  • Fatty Acids, Monounsaturated
  • Immunoglobulin G
  • Liposomes
  • Phosphatidylethanolamines
  • Quaternary Ammonium Compounds
  • Vaccines
  • Polyethylene Glycols
  • Ovalbumin
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane