Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants
Archaeosomes are liposomes comprised of ether lipids derived from various archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses and enhance protect...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2017.1423154 |
| _version_ | 1797677477604098048 |
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| author | Bassel Akache Felicity C. Stark Umar Iqbal Wangxue Chen Yimei Jia Lakshmi Krishnan Michael J. McCluskie |
| author_facet | Bassel Akache Felicity C. Stark Umar Iqbal Wangxue Chen Yimei Jia Lakshmi Krishnan Michael J. McCluskie |
| author_sort | Bassel Akache |
| collection | DOAJ |
| description | Archaeosomes are liposomes comprised of ether lipids derived from various archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Archaeosomes constituted with total polar lipids (TPL) of various archaea are relatively complex, comprising >10 different lipid compounds. Archaeosomes can be constituted with semi-synthetic glycerolipids built on ether-linked isoprenoid phytanyl cores with varied synthetic glycol- and amino-head groups. However, such 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 saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) mixed with uncharged glycolipid (lactosylarchaeol, LA). This new class of adjuvants can be easily synthesized and retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we demonstrate the safety of SLA/LA archaeosomes following intramuscular injection to mice and evaluate the immunogenicity, in vivo distribution and cellular uptake of antigen (ovalbumin) encapsulated into SLA/LA archaeosomes. Overall, we have found that semi-synthetic sulfated glycolipid archaeosomes are a safe and effective novel class of adjuvants capable of inducing strong antigen-specific immune responses in mice and protection against subsequent B16 melanoma tumor challenge. A key step in their mechanism of action appears to be the recruitment of immune cells to the injection site and the subsequent trafficking of antigen to local draining lymph nodes. |
| first_indexed | 2024-03-11T22:45:42Z |
| format | Article |
| id | doaj.art-63424f4b264f4f388d085f8757db0a94 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:45:42Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-63424f4b264f4f388d085f8757db0a942023-09-22T08:17:54ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2018-07-011471746175910.1080/21645515.2017.14231541423154Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvantsBassel Akache0Felicity C. Stark1Umar Iqbal2Wangxue Chen3Yimei Jia4Lakshmi Krishnan5Michael J. McCluskie6Human Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaHuman Health Therapeutics, National Research Council CanadaArchaeosomes are liposomes comprised of ether lipids derived from various archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Archaeosomes constituted with total polar lipids (TPL) of various archaea are relatively complex, comprising >10 different lipid compounds. Archaeosomes can be constituted with semi-synthetic glycerolipids built on ether-linked isoprenoid phytanyl cores with varied synthetic glycol- and amino-head groups. However, such 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 saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) mixed with uncharged glycolipid (lactosylarchaeol, LA). This new class of adjuvants can be easily synthesized and retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we demonstrate the safety of SLA/LA archaeosomes following intramuscular injection to mice and evaluate the immunogenicity, in vivo distribution and cellular uptake of antigen (ovalbumin) encapsulated into SLA/LA archaeosomes. Overall, we have found that semi-synthetic sulfated glycolipid archaeosomes are a safe and effective novel class of adjuvants capable of inducing strong antigen-specific immune responses in mice and protection against subsequent B16 melanoma tumor challenge. A key step in their mechanism of action appears to be the recruitment of immune cells to the injection site and the subsequent trafficking of antigen to local draining lymph nodes.http://dx.doi.org/10.1080/21645515.2017.1423154adjuvantsadjuvantsarchaeosomesdeliveryglycolipidimmune modulatorssafetyvaccinevaccinology |
| spellingShingle | Bassel Akache Felicity C. Stark Umar Iqbal Wangxue Chen Yimei Jia Lakshmi Krishnan Michael J. McCluskie Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants Human Vaccines & Immunotherapeutics adjuvants adjuvants archaeosomes delivery glycolipid immune modulators safety vaccine vaccinology |
| title | Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| title_full | Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| title_fullStr | Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| title_full_unstemmed | Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| title_short | Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| title_sort | safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants |
| topic | adjuvants adjuvants archaeosomes delivery glycolipid immune modulators safety vaccine vaccinology |
| url | http://dx.doi.org/10.1080/21645515.2017.1423154 |
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