Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Adjuvants, Immunologic*; Glyceryl Ethers/*immunology ; Glycolipids/*immunology ; Halobacterium salinarum/*chemistry ; Immunity, Cellular/*drug effects ; Liposomes/*immunology ; Vaccines/*immunology; Animals ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Glyceryl Ethers/administration & dosage ; Glyceryl Ethers/chemistry ; Glycolipids/administration & dosage ; Glycolipids/chemistry ; Hepatitis B Surface Antigens/administration & dosage ; Hepatitis B Surface Antigens/immunology ; Immunogenicity, Vaccine ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Liposomes/administration & dosage ; Liposomes/chemistry ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Animal ; Ovalbumin ; Serologic Tests ; Vaccines/administration & dosage ; Vaccines/chemistry
    • Abstract:
      Archaeosomes are liposomes traditionally comprised of total polar lipids (TPL) or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glyco- and amino-head groups. As adjuvants, they induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Traditional total polar lipid (TPL) archaeosome formulations are relatively complex and first generation semi-synthetic archaeosomes involve many synthetic steps to arrive at the final desired glycolipid composition. We have developed a novel archaeosome formulation comprising a sulfated disaccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) that can be more readily synthesized yet retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we have evaluated the immunostimulatory effects of SLA archaeosomes when used as adjuvant with ovalbumin (OVA) and hepatitis B surface antigen (HBsAg) and compared this to various other adjuvants including TLR3/4/9 agonists, oil-in-water and water-in-oil emulsions and aluminum hydroxide. Overall, we found that semi-synthetic sulfated glycolipid archaeosomes induce strong Ag-specific IgG titers and CD8 T cells to both antigens. In addition, they induce the expression of a number of cytokines/chemokines including IL-6, G-CSF, KC & MIP-2. SLA archaeosome formulations demonstrated strong adjuvant activity, superior to many of the other tested adjuvants.
      Competing Interests: Lakshmi Krishnan is an inventor on various archaeosome patents and patent applications, namely 1) Sulfated-glycolipids as adjuvants for vaccines (WO2016004512A1), 2) Synthetic archaeal glycolipid adjuvants (WO2007112567A1) & 3) Archaeosomes as adjuvants and carriers for acellular vaccines to induce cytotoxic t lymphocyte (ctl) responses (WO2001026683A2). All other authors state no conflict of interest, nor competing financial interests. There are no products in development or marketed products to declare.
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    • Accession Number:
      0 (Adjuvants, Immunologic)
      0 (Cytokines)
      0 (Glyceryl Ethers)
      0 (Glycolipids)
      0 (Hepatitis B Surface Antigens)
      0 (Immunoglobulin G)
      0 (Liposomes)
      0 (Vaccines)
      0 (archaeol lipid)
      0 (sulfoglycolipids)
      9006-59-1 (Ovalbumin)
    • Publication Date:
      Date Created: 20181205 Date Completed: 20190606 Latest Revision: 20200309
    • Publication Date:
      20240105
    • Accession Number:
      PMC6279041
    • Accession Number:
      10.1371/journal.pone.0208067
    • Accession Number:
      30513093