Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice

被引：31

作者：

Akache, Bassel ^{[1
]}

Stark, Felicity C. ^{[1
]}

Jia, Yimei ^{[1
]}

Deschatelets, Lise ^{[1
]}

Dudani, Renu ^{[1
]}

Harrison, Blair A. ^{[1
]}

Agbayani, Gerard ^{[1
,2
]}

Williams, Dean ^{[1
]}

Jamshidi, Mohammad P. ^{[1
]}

Krishnan, Lakshmi ^{[1
,2
]}

McCluskie, Michael J. ^{[1
]}

机构：

[1] Natl Res Council Canada, Ottawa, ON, Canada

[2] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada

来源：

PLOS ONE | 2018年 / 13卷 / 12期

关键词：

HEPATITIS-B-VACCINE; T-CELL RESPONSES; ANTIGEN; RECOGNITION; IMMUNOGENICITY; IMMUNIZATION; INDUCTION; LIPOSOMES; INFECTION; IMMUNITY;

D O I：

10.1371/journal.pone.0208067

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Archaeosomes are liposomes traditionally comprised of total polar lipids (TPL) or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glyco- and aminohead 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.

引用

页数：25

共 51 条

[1]

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