Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein

J Control Release. 2018 Sep 10:285:12-22. doi: 10.1016/j.jconrel.2018.06.028. Epub 2018 Jun 28.

Abstract

Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes) show promising potential as vaccine delivery systems. Their unique internal structure, composed of both lipophilic domains and water-containing channels, renders them capable of accommodating immunopotentiating compounds and antigens. However, their adjuvant properties are poorly understood. We hypothesized that the supramolecular structure of the lyotropic liquid crystalline phase influences the immunostimulatory activity of lipid-based nanocarriers. To test this, hexosomes were designed containing the lipid phytantriol (Phy) and the immunopotentiator monomycoloyl glycerol-1 (MMG-1). Self-assembly of Phy and MMG-1 into nanocarriers featuring an internal hexagonal phase was confirmed by small-angle X-ray scattering and cryogenic transmission electron microscopy. The effect of the nanostructure on the adjuvant activity was studied by comparing the immunogenicity of Phy/MMG-1 hexosomes with MMG-1-containing lamellar liquid crystalline nanoparticles (liposomes, CAF04). The quality and magnitude of the elicited immune responses were determined after vaccination of CB6/F1 mice using the Chlamydia trachomatis major outer membrane protein (MOMP) as antigen. MMG-1-based hexosomes potentiated significantly stronger MOMP-specific humoral responses than CAF04 liposomes. The liposome-based vaccine formulation induced a much stronger MOMP-specific cell-mediated immune response compared to hexosome-adjuvanted MOMP, which elicited minimal MOMP-specific T-cell stimulation after vaccination. Hence, our data demonstrates that hexosomal and liposomal adjuvants activate the immune system via different mechanisms. Our work provides valuable insights into the adjuvant potential of hexosomes and emphasizes that engineering of the supramolecular structure can be used to design adjuvants with customized immunological properties.

Keywords: Adjuvant; Hexosomes; Liposomes; Monomycoloyl glycerol; Nanostructure; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibody Formation / drug effects
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / pharmacology*
  • Chlamydia Infections / immunology
  • Chlamydia Infections / prevention & control*
  • Chlamydia trachomatis / immunology*
  • Drug Carriers / chemistry
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology*
  • Female
  • Liquid Crystals / chemistry
  • Mice
  • Monoglycerides / administration & dosage
  • Monoglycerides / chemistry
  • Monoglycerides / pharmacology*
  • Nanoparticles / chemistry
  • Porins / administration & dosage
  • Porins / pharmacology*
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Bacterial Vaccines
  • Drug Carriers
  • Fatty Alcohols
  • Monoglycerides
  • Porins
  • monomycoloyl glycerol
  • omp1 protein, Chlamydia trachomatis
  • 3,7,11,15-tetramethyl-1,2,3-hexadecanetriol