Archaeosome adjuvants: immunological capabilities and mechanism(s) of action.
Archaeosomes (liposomes comprised of glycerolipids of Archaea) constitute potent adjuvants for the induction of Th1, Th2 and CD8(+) T cell responses to the entrapped soluble antigen. Archaeal lipids are uniquely constituted of ether-linked isoprenoid phytanyl cores conferring stability to the membranes. Additionally, varied head groups displayed on the glycerol-lipid cores facilitate unique immunostimulating interactions with mammalian antigen-presenting cells (APCs). The polar lipid from the archaeon, Methanobrevibacter smithii has been well characterized for its adjuvant potential, and is abundant in archaetidyl serine, promoting interaction with a phosphatidylserine receptor on APCs. These archaeosomes mediate MHC class I cross-priming via the phagosome-to-cytosol TAP-dependent classical processing pathway, and also upregulate costimulation by APCs without overt inflammatory cytokine production. Furthermore, they facilitate potent CD8(+) T cell memory to co-delivered antigen, comparable in magnitude and quality to live bacterial vaccine vectors. Archaeosome vaccines provide profound protection in murine models of infection and cancer. This technology is being developed for clinical application and offers a novel prospect for rational design and development of safe and potent subunit vaccines capable of eliciting T cell immunity against intracellular infections and cancers.
Krishnan
Lakshmi
L
National Research Council-Institute for Biological Sciences, Ottawa, ON, Canada K1A 0R6. Lakshmi.Krishnan@nrc-cnrc.gc.ca
Sprott
G Dennis
GD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000277:Adjuvants, Pharmaceutic; D017951:Antigen Presentation; D001105:Archaea / Q000737:chemistry* / Q000276:immunology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016503:Drug Delivery Systems; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D008055:Lipids; D008081:Liposomes; D014612:Vaccines