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
Authors:
- Letícia Rodrigues,
- Konstantinos N. Raftopoulos,
- Signe Tandrup Schmidt,
- Fabian Schneider,
- Hendrik Dietz,
- Thomas Rades,
- Henrik Franzyk,
- Anders Elm Pedersen,
- Christine M. Papadakis,
- Dennis Christensen,
- Gerhard Winter,
- Camilla Foged,
- Madlen Hubert
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.
- Record ID
- CUT9e4112db7d98444f8747cbeb22903edc
- Publication categories
- ;
- Author
- Journal series
- Journal of Controlled Release, ISSN 0168-3659, e-ISSN 1873-4995
- Issue year
- 2018
- Vol
- 285
- Pages
- 12-22
- Other elements of collation
- fot.; schem.; tab.; wykr.; Bibliografia (na s.) - 21-22; Bibliografia (liczba pozycji) - 42; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 285
- Keywords in English
- adjuvant, hexosomes, liposomes, monomycoloyl glycerol, nanostructure, vaccine, glycerol oleate, liquid crystals, polarization microscopy
- DOI
- DOI:10.1016/j.jconrel.2018.06.028 Opening in a new tab
- URL
- https://www.sciencedirect.com/science/article/pii/S0168365918303766 Opening in a new tab
- Language
- eng (en) English
- Score (nominal)
- 45
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUT9e4112db7d98444f8747cbeb22903edc/
- URN
urn:pkr-prod:CUT9e4112db7d98444f8747cbeb22903edc
* presented citation count is obtained through Internet information analysis, and it is close to the number calculated by the Publish or PerishOpening in a new tab system.