Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice
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 pro...
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| Veröffentlicht in: | PloS one 2018-12, Vol.13 (12), p.e0208067-e0208067 |
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| creator | Akache, Bassel Stark, Felicity C Jia, Yimei Deschatelets, Lise Dudani, Renu Harrison, Blair A Agbayani, Gerard Williams, Dean Jamshidi, Mohammad P Krishnan, Lakshmi McCluskie, Michael J |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0208067 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0208067</identifier><identifier>PMID: 30513093</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvant drugs ; Adjuvants ; Adjuvants, Immunologic ; Albumin ; Aluminum ; Aluminum compounds ; Aluminum hydroxide ; Animal models ; Animals ; Antigens ; Biochemistry ; Biology and Life Sciences ; Cancer ; Cancer prevention ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell-mediated immunity ; Chemical properties ; Chemokines ; Communicable diseases ; Councils ; Cytokines ; Cytokines - immunology ; Cytokines - metabolism ; Disaccharides ; Emulsions ; Female ; Formulations ; Glyceryl Ethers - administration & dosage ; Glyceryl Ethers - chemistry ; Glyceryl Ethers - immunology ; Glycolipid composition ; Glycolipids ; Glycolipids - administration & dosage ; Glycolipids - chemistry ; Glycolipids - immunology ; Granulocyte colony-stimulating factor ; Halobacterium salinarum - chemistry ; Hepatitis ; Hepatitis B ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - administration & dosage ; Hepatitis B Surface Antigens - immunology ; Hydroxides ; Immune response ; Immune response (cell-mediated) ; Immune response (humoral) ; Immunity ; Immunity, Cellular - drug effects ; Immunization ; Immunogenicity, Vaccine ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Immunology ; Immunostimulation ; Infectious diseases ; Interleukin 6 ; Lipids ; Liposomes ; Liposomes - administration & dosage ; Liposomes - chemistry ; Liposomes - immunology ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Membrane lipids ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Animal ; Older people ; Ovalbumin ; People and Places ; Phospholipids ; Plant lipids ; Research and Analysis Methods ; Serologic Tests ; Sulfates ; T cells ; Tumors ; Vaccines ; Vaccines - administration & dosage ; Vaccines - chemistry ; Vaccines - immunology</subject><ispartof>PloS one, 2018-12, Vol.13 (12), p.e0208067-e0208067</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Akache et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Akache et al 2018 Akache et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1eb6bae2266f18c212f3f0730d8bd684f1b5e1cfb449493a9d91996bdec810983</citedby><cites>FETCH-LOGICAL-c692t-1eb6bae2266f18c212f3f0730d8bd684f1b5e1cfb449493a9d91996bdec810983</cites><orcidid>0000-0002-5377-7193</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279041/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279041/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30513093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Murthy, Ashlesh K.</contributor><creatorcontrib>Akache, Bassel</creatorcontrib><creatorcontrib>Stark, Felicity C</creatorcontrib><creatorcontrib>Jia, Yimei</creatorcontrib><creatorcontrib>Deschatelets, Lise</creatorcontrib><creatorcontrib>Dudani, Renu</creatorcontrib><creatorcontrib>Harrison, Blair A</creatorcontrib><creatorcontrib>Agbayani, Gerard</creatorcontrib><creatorcontrib>Williams, Dean</creatorcontrib><creatorcontrib>Jamshidi, Mohammad P</creatorcontrib><creatorcontrib>Krishnan, Lakshmi</creatorcontrib><creatorcontrib>McCluskie, Michael J</creatorcontrib><title>Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Adjuvant drugs</subject><subject>Adjuvants</subject><subject>Adjuvants, Immunologic</subject><subject>Albumin</subject><subject>Aluminum</subject><subject>Aluminum compounds</subject><subject>Aluminum hydroxide</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Cancer prevention</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell-mediated immunity</subject><subject>Chemical properties</subject><subject>Chemokines</subject><subject>Communicable diseases</subject><subject>Councils</subject><subject>Cytokines</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>Disaccharides</subject><subject>Emulsions</subject><subject>Female</subject><subject>Formulations</subject><subject>Glyceryl Ethers - administration & dosage</subject><subject>Glyceryl Ethers - chemistry</subject><subject>Glyceryl Ethers - immunology</subject><subject>Glycolipid composition</subject><subject>Glycolipids</subject><subject>Glycolipids - administration & dosage</subject><subject>Glycolipids - chemistry</subject><subject>Glycolipids - immunology</subject><subject>Granulocyte colony-stimulating factor</subject><subject>Halobacterium salinarum - chemistry</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - administration & dosage</subject><subject>Hepatitis B Surface Antigens - immunology</subject><subject>Hydroxides</subject><subject>Immune response</subject><subject>Immune response (cell-mediated)</subject><subject>Immune response (humoral)</subject><subject>Immunity</subject><subject>Immunity, Cellular - drug effects</subject><subject>Immunization</subject><subject>Immunogenicity, Vaccine</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunology</subject><subject>Immunostimulation</subject><subject>Infectious diseases</subject><subject>Interleukin 6</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Liposomes - administration & dosage</subject><subject>Liposomes - chemistry</subject><subject>Liposomes - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine and Health Sciences</subject><subject>Membrane lipids</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Animal</subject><subject>Older people</subject><subject>Ovalbumin</subject><subject>People and Places</subject><subject>Phospholipids</subject><subject>Plant lipids</subject><subject>Research and Analysis Methods</subject><subject>Serologic Tests</subject><subject>Sulfates</subject><subject>T cells</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>Vaccines - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akache, Bassel</au><au>Stark, Felicity C</au><au>Jia, Yimei</au><au>Deschatelets, Lise</au><au>Dudani, Renu</au><au>Harrison, Blair A</au><au>Agbayani, Gerard</au><au>Williams, Dean</au><au>Jamshidi, Mohammad P</au><au>Krishnan, Lakshmi</au><au>McCluskie, Michael J</au><au>Murthy, Ashlesh K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-12-04</date><risdate>2018</risdate><volume>13</volume><issue>12</issue><spage>e0208067</spage><epage>e0208067</epage><pages>e0208067-e0208067</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30513093</pmid><doi>10.1371/journal.pone.0208067</doi><tpages>e0208067</tpages><orcidid>https://orcid.org/0000-0002-5377-7193</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-12, Vol.13 (12), p.e0208067-e0208067 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2149884595 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adjuvant drugs Adjuvants Adjuvants, Immunologic Albumin Aluminum Aluminum compounds Aluminum hydroxide Animal models Animals Antigens Biochemistry Biology and Life Sciences Cancer Cancer prevention CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell-mediated immunity Chemical properties Chemokines Communicable diseases Councils Cytokines Cytokines - immunology Cytokines - metabolism Disaccharides Emulsions Female Formulations Glyceryl Ethers - administration & dosage Glyceryl Ethers - chemistry Glyceryl Ethers - immunology Glycolipid composition Glycolipids Glycolipids - administration & dosage Glycolipids - chemistry Glycolipids - immunology Granulocyte colony-stimulating factor Halobacterium salinarum - chemistry Hepatitis Hepatitis B Hepatitis B surface antigen Hepatitis B Surface Antigens - administration & dosage Hepatitis B Surface Antigens - immunology Hydroxides Immune response Immune response (cell-mediated) Immune response (humoral) Immunity Immunity, Cellular - drug effects Immunization Immunogenicity, Vaccine Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Immunology Immunostimulation Infectious diseases Interleukin 6 Lipids Liposomes Liposomes - administration & dosage Liposomes - chemistry Liposomes - immunology Lymphocytes Lymphocytes T Medicine and Health Sciences Membrane lipids Mice Mice, Inbred BALB C Mice, Inbred C57BL Models, Animal Older people Ovalbumin People and Places Phospholipids Plant lipids Research and Analysis Methods Serologic Tests Sulfates T cells Tumors Vaccines Vaccines - administration & dosage Vaccines - chemistry Vaccines - immunology |
| title | Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice |
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