Development of new glycosylation methodologies for the synthesis of archaeal-derived glycolipid adjuvants

Whitfield, Dennis M.; Yu, Siu Hong; Dicaire, Chantale J.; Sprott, G. Dennis

doi:10.1016/j.carres.2009.10.011

Cited by 33 publications

(22 citation statements)

References 48 publications

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“…PGP archaeosomes direct antigen primarily to an antibody pathway of response as suggested previously [10]. Additions of glycoarchaeols to PGP archaeosomes enhance greatly the MHC class I pathway of antigen presentation producing the CD8 + T cell response.…”

Section: Discussionmentioning

confidence: 67%

“…Mannotriosylarchaeol, maltotriosylarchaeol, gentiobiosylarchaeol, and gentiotriosylarchaeol were synthesized according to our previous descriptions [10, 16] and structural details are shown in Figure 1. Synthesis methods for archaetidylserine can be found in Supplementary Material available online at doi:10.1155/2012/513231.…”

Section: Methodsmentioning

confidence: 99%

“…Recently archaeol has been isolated from hydrolysed polar lipid extracts of Halobacterium salinarum to use as the lipid precursor to chemically synthesize various polar lipids, including glycolipids [9, 10]. The lipids so generated are described as synthetic or more precisely as semisynthetic, because the lipid moiety with specific archaeal sn-2,3 and R-methyl group stereochemistry is of biological origin, whereas a polar head group may be conjugated to the free sn-1 hydroxyl of the glycerol backbone to give a new polar lipid structure.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Archaeosome Vaccines Containing Triglycosylarchaeols Can Provide Additive and Long-Lasting Immune Responses That Are Enhanced by Archaetidylserine

Sprott

Yeung

Dicaire

et al. 2012

Archaea

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The relation between archaeal lipid structures and their activity as adjuvants may be defined and explored by synthesizing novel head groups covalently linked to archaeol (2,3-diphytanyl-sn-glycerol). Saturated archaeol, that is suitably stable as a precursor for chemical synthesis, was obtained in high yield from Halobacterium salinarum. Archaeosomes consisting of the various combinations of synthesized lipids, with antigen entrapped, were used to immunize mice and subsequently determine CD8+ and CD4+-T cell immune responses. Addition of 45 mol% of the glycolipids gentiotriosylarchaeol, mannotriosylarchaeol or maltotriosylarchaeol to an archaetidylglycerophosphate-O-methyl archaeosome, significantly enhanced the CD8+ T cell response to antigen, but diminished the antibody titres in peripheral blood. Archaeosomes consisting of all three triglycosyl archaeols combined with archaetidylglycerophosphate-O-methyl (15/15/15/55 mol%) resulted in approximately additive CD8+ T cell responses and also an antibody response not significantly different from the archaetidylglycerophosphate-O-methyl alone. Synthetic archaetidylserine played a role to further enhance the CD8+ T cell response where the optimum content was 20–30 mol%. Vaccines giving best protection against solid tumor growth corresponded to the archaeosome adjuvant composition that gave highest immune activity in immunized mice.

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Section: Discussionmentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthetic Archaeosome Vaccines Containing Triglycosylarchaeols Can Provide Additive and Long-Lasting Immune Responses That Are Enhanced by Archaetidylserine

Sprott

Yeung

Dicaire

et al. 2012

Archaea

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“…Semi-synthetic archaeosome lipids were prepared by first purifying archaeol from Halobacterium salinarum (ATCC 33170, Manassas, VA, USA) and using it as a building block to attach a synthetic head-group, sulfated lactose. The resulting lipid was sulfated lactosyl archaeol (SLA; 6'-sulfate-β-D-Galp-(1,4)-β-D-Glcp-(1,1)-archaeol) and was synthesized as described previously [22,23]. M. smithii (MS) total polar lipids were extracted as described previously [22,24,25].…”

Section: Vaccine Preparation and Route Of Immunizationmentioning

confidence: 99%

“…The resulting lipid was sulfated lactosyl archaeol (SLA; 6'-sulfate-β-D-Galp-(1,4)-β-D-Glcp-(1,1)-archaeol) and was synthesized as described previously [22,23]. M. smithii (MS) total polar lipids were extracted as described previously [22,24,25]. SLA archaeosomes were formed and simply admixed with OVA, hereafter referred to as SLA-OVA (adm) as described previously [26].…”

Section: Vaccine Preparation and Route Of Immunizationmentioning

confidence: 99%

Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma

et al. 2019

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Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that when used as adjuvants induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigens. However, traditional entrapped archaeosome formulations have only low entrapment efficiency, therefore we have developed a novel admixed formulation which offers many advantages, including reduced loss of antigen, consistency of batch-to-batch production as well as providing the option to formulate the vaccine immediately before use, which is beneficial for next generation cancer therapy platforms that include patient specific neo-antigens or for use with antigens that are less stable. Herein, we demonstrate that, when used in combination with anti-CTLA-4 and anti-PD-1 checkpoint therapy, this novel admixed archaeosome formulation, comprised of preformed sulfated lactosyl archaeol (SLA) archaeosomes admixed with OVA antigen (SLA–OVA (adm)), was as effective at inducing strong CD8+ T cell responses and protection from a B16-OVA melanoma tumor challenge as the traditionally formulated archaeosomes with encapsulated OVA protein. Furthermore, archaeosome vaccine formulations combined with anti-CTLA-4 and anti-PD-1 therapy, induced OVA-CD8+ T cells within the tumor and immunohistochemical analysis revealed the presence of CD8+ T cells associated with dying or dead tumor cells as well as within or around tumor blood vessels. Overall, archaeosomes constitute an attractive option for use with combinatorial checkpoint inhibitor cancer therapy platforms.

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Archaeal Membrane Lipids and Applications

Sprott¹

2011

Encyclopedia of Life Sciences

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Membrane lipids of Archaea are unique and distinct from those found in Eukarya and Bacteria . The polar lipids consist of isoprenoid chains, 20–40 carbons in length and usually saturated, which are attached via stable ether bonds to the glycerol carbons at the sn ‐2,3 positions. Polar head groups differ at the genus level of diversity and consist of mixtures of glyco groups (mainly disaccharides), and/or phospho groups primarily phosphoglycerol, phosphoserine, phosphoethanolamine or phosphoinositol. Phosphocholine headgroups are rarely found. Extremely halophilic archaea are characterised by headgroups consisting of phosphoglycerolphosphate‐ O ‐methyl, and sulfated‐sugars. Some of these archaea synthesise cardiolipin analogues. The inherent stability and unique features of archaeal lipids makes them a useful biomarker for Archaea within environmental samples, including ocean sediments. The polar lipids of Archaea can be used to make liposomes (closed vesicles referred to as archaeosomes) with characteristics that are useful for applications in biotechnology. Archaeal‐like polar lipids are being synthesised to optimise the properties of archaeosomes to serve as next‐generation adjuvants and drug delivery systems. Key Concepts: Archaeol (2,3‐diphytanyl‐ sn ‐glycerol), and variations thereof, define the polar lipids of the domain of life, Archaea . The structures of polar lipids biosynthesised provide a useful taxonomic feature to assign an isolate to the Genus level of classification. New polar lipid structures are being reported as the field expands to encompass novel isolates. These unique polar and neutral isoprenyl lipids can be used as biomarkers of archaea in environmental samples. Archaeal lipids can serve as a rich source for novel molecules not commonly found in nature, such as β‐ l ‐gulose. Archaeal polar lipid mixtures hydrate to form lipid membrane vesicles (archaeosomes) with bilayer, unilayer or a combination of uni and bilayer structure. Archaeosomes are generally nonfusogenic in vitro , but fusion can be dramatic for certain compositions by exposure to the combination of acidic pH, calcium and glycosidase. Archaeosomes function as safe vaccine adjuvants in mammals imparting long‐lasting CD8 + T‐cell immunity and antibody responses. Isoprenoid lipids that retain the key archaeal‐lipid features are being synthesised to optimise their properties as vaccine adjuvants and delivery systems.

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Development of new glycosylation methodologies for the synthesis of archaeal-derived glycolipid adjuvants

Cited by 33 publications

References 48 publications

Synthetic Archaeosome Vaccines Containing Triglycosylarchaeols Can Provide Additive and Long-Lasting Immune Responses That Are Enhanced by Archaetidylserine

Synthetic Archaeosome Vaccines Containing Triglycosylarchaeols Can Provide Additive and Long-Lasting Immune Responses That Are Enhanced by Archaetidylserine

Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma

Archaeal Membrane Lipids and Applications

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