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

Sprott, G. Dennis; Yeung, Angela; Dicaire, Chantal J.; Yu, Siu Hong; Whitfield, Dennis M.

doi:10.1155/2012/513231

Cited by 32 publications

(30 citation statements)

References 26 publications

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“…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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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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“…In particular, archaeosomes are thermally resistant and can maintain entrapment integrity even when autoclaved 9 . Archaeosomes are also more susceptible to uptake by phagocytic cells than liposomes of ester phospholipids 10 leading to their utility as adjuvants in the development of antibodies 2,11,12 . The wider use of archaeosomes is directly limited by availability of archaeal lipids derived as mixtures from natural sources 7 .…”

Section: R a F Tmentioning

confidence: 99%

A membrane-spanning macrocyclic bolaamphiphile lipid mimic of archaeal lipids

et al. 2017

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The synthesis of a 72-membered macrocyclic tetraester bolaamphiphile is accomplished in six chemical steps from commercially available starting materials using copper-accelerated azide–alkyne coupling to close the macrocycle in high yield. Related diester amphiphiles and an acyclic tetraester bolaamphiphile were also prepared. The set of lipids bearing nitrophenyl phosphate head groups were incorporated into phospholipid vesicles but failed to undergo phosphate hydrolysis in basic conditions, undergoing efficient elimination in competition. The same lipid cores bearing phosphate-linked nitrobenzoxadiazole (NBD) head groups also incorporated into phospholipid vesicles and the NBD fluorescence was quenched with cobalt ions. The proportion of membrane-spanning bolaamphiphiles was determined from the ratio of cobalt quenching in the presence and in the absence of a detergent. The macrocyclic bolaamphiphile is incorporated into phospholipid vesicles such that 48 ± 4% of the NBD head groups are in the outer leaflet, consistent with a membrane-spanning orientation. The acyclic bolaamphiphile is incorporated with 75 ± 3% of the NBD head groups accessible to quencher in the absence of a detergent suggesting U-shaped incorporation in the outer leaflet of the bilayer membrane. In ring size and spanning ability, the macrocyclic bolaamphiphile mimics naturally occurring macrocyclic archaeal lipids.

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“…Interestingly, a novel SLA archaeosome formulation, whereby the antigen is simply admixed with preformed SLA archaeosomes, has also been shown to stimulate equal or superior antigen-specific responses as formulations where the antigen is entrapped within the archaeosome [20]. As the efficiency of antigen entrapment within archaeosomes formulations is typically variable and relatively low (5-40%) [21,22], this new admixed formulation provides a convenient easy to mix format with no loss of antigen during the formulation process, thereby reducing costs and standardizing the amount of archaeal lipid in the final vaccine formulations.…”

Section: Introductionmentioning

confidence: 99%

Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

et al. 2019

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Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested.

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

Cited by 32 publications

References 26 publications

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

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

A membrane-spanning macrocyclic bolaamphiphile lipid mimic of archaeal lipids

Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

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