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Chapter 23 : Archaeosome Vaccines

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Archaeosome Vaccines, Page 1 of 2

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Abstract:

Archaeosomes have been developed from various archaea for use as drug delivery systems and vaccine applications that utilize their adjuvant properties. This chapter describes the mechanism of archaeosome adjuvants as self-adjuvanting antigen carrier systems that are taken up by specific receptor-mediated endocytosis to promote both CD4 and CD8 T-cell responses. Effects of lipid structure on the immune response are also reviewed in this chapter. Archaeal lipids possess several features that make them ideal for the preparation of archaeosomes. The first is the inherent stability of the polar lipids. Second, archaeal lipids form archaeosomes over physiological temperature ranges, allowing preparation of vaccines at ambient temperatures. Third, once formed, archaeosomes of 50 to 250-nm diameters remain suspended indefinitely and resist fusion or aggregation over long storage periods. Two signals are required to activate T cells. The first is antigen presentation in the context of MHC, and the second is costimulation of the specific T cell recognizing the presented antigen. Several lines of evidence support a phosphatidylserine (PS) receptormediated endocytic mechanism. Data using test antigens indicate the strong potential for archaeosome vaccines to achieve immunity against intracellular bacteria. Because is an intracellular pathogen that is typically cleared by the host CD8 T-cell immunity, this model has been used as a test for potency of archaeosome vaccines.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23

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MHC Class I
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MHC Class II
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Cytotoxic T Cell
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Tumor Necrosis Factor
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Figures

Image of Figure 1.
Figure 1.

Archaeol and caldarchaeol polar lipid membrane models. (A) Model lipids are archaetidylglycerol arranged to depict a bilayer archaeosome membrane. Regular methyl branches of the isopranoid chains are shown. (B) The membrane is depicted as a unilayer composed of the main polar lipid of ( ). (C) This model of an archaeosome membrane consists of a mixture of A and B polar lipids.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 2.
Figure 2.

Correlation between the caldarchaeol content of archaeal membranes and the frequency of intramembrane fractures observed by freeze-fracture electron microscopy. Similar data were obtained for freeze-fractured archaeosomes prepared from the total polar lipids extracted from the same archaea. Modified from the ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 3.
Figure 3.

Correlation between the caldarchaeol content of archaeosomes and their thermal stabilities. Carboxyfluorescein (CF) was entrapped within archaeosomes made of total polar lipids from (Mm), (Mst), (Ms), (Mj), (Mh), (Me), and (Ta). Retention of CF was measured following autoclaving for 15 min at 121°C. Modified from the ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 4.
Figure 4.

Proton and glycerol permeabilities of liposomes and archaeosomes. Permeability rates were measured in lipid vesicles prepared from the ester lipid diphytanylphosphatidylcholine (Dph-PC), total polar lipids of (As), (As + Co), (Am + Co + As), and (Cp + As). Symbols indicate archaeols (As), caldarchaeols (Cs), macrocyclic archaeols (Am), and caldarchaeols with cyclopentane rings (Cp). Reproduced from the ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 5.
Figure 5.

Uptake of fluorescent archaeosomes by phagocytic cells. Archaeosomes composed of total polar lipids were prepared either by incorporating a small amount of the fluorescent lipid rhodamine-phosphatidylethanolamine ( ) or by entrapping 1.5 mM carboxyfluorescein ( ). Uptake was performed in 1 ml of RPMI medium added to 0.5 million adhered cells ( ). Panels show 30-min uptakes: (A) rhodamine-archaeosomes (100 μg) by thioglycollate-activated mouse peritoneal macrophages; (B) uptake of rhodamine-archaeosomes (25 μg) by bone marrow-derived DCs; (C) uptake of carboxyfluorescein-archaeosomes (40 μg) by macrophages culture J774A.1; and (D) uptake of rhodamine-archaeosomes (100 μg) by thioglycollate-activated mouse peritoneal macrophages.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 6.
Figure 6.

Structures and abundance of the polar lipids found in the total polar lipids of ( ). Phosphoserine head-groups are abundant in both archaeol (2,3-di---phytanylglycerol) and its dimer, caldarchaeol, lipids. Other lipids present in minor amounts are not shown.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 7.
Figure 7.

Upregulation of cell surface molecules on J774A.1 macrophages treated with archaeosomes. Macrophages were treated for 24 h, with no activator, 25 μg of antigen-free liposomes ml (PC/PG/cholesterol), 25 μg of antigen-free archaeosomes ml, or 10 μg of lipopolysaccharide ml. Cells were then double stained with Mac1α-PE (macrophages marker) and one of the cell surface markers shown. Data were acquired by flow cytometry. Reproduced from the ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 8.
Figure 8.

Scheme depicting processing of ovalbumin encapsulated in archaeosomes of by an APC. Sites of inhibitor action are shown. Specific peptide fragments of the Ag (ovalbumin) are presented by MHC class I or MHC class II to CD8 T cells and CD4 T cells, respectively. A CD8 T cell specific to the MHC class I ovalbumin peptide complex is shown docking with the APC. Docking results in activation and excretion of IL-2 and IFN-γ. SR, signaling receptor; PR, phagocytosis receptor; R1, R2, and R3 are steps 1 to 3, the rate of which depend on the archaeosome composition and APC.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 9.
Figure 9.

PS receptor-mediated endocytosis of archaeosomes containing ovalbumin. Processing of ovalbumin and presentation of peptide by MHC class I is quantified by assay of IL-2 or IFN-γ by activated CD8 T cells, as described in the legend to Fig. 8 . Competition for uptake of archaeosomes was assayed for soluble phospho-L-serine (Sol. PS), phosphatidylserine liposomes (PS lipo), or mannopentaose (MP), at the μg concentrations shown in parentheses. Reproduced from the ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 10.
Figure 10.

Influence of the polar lipid composition of archaeosomes on humoral adjuvant activity. Archaeosomes with entrapped ovalbumin were prepared from the total polar lipids extracted from (H.h), strains 14039 and 16008, (M.m), (M.s), and (M.j). Injections, given subcutaneously at zero and 3 weeks, contained 15 μg ovalbumin. Titers of antiovalbumin antibody in sera are given for 10-day and 49-day bleeds. Titers in sera from mice immunized with 15 μg ovalbumin (no adjuvant) were below 10. Each data point is for a different mouse. Reproduced from ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 11.
Figure 11.

Influence of the polar lipid composition on cytotoxic T-cell responses (CTL) to ovalbumin entrapped in archaeosomes. C57Bl/6 mice were immunized subcutaneously with 15 μg ovalbumin entrapped in various total polar lipid archaeosomes. Ten days later, CTL activity was measured in splenic cell cultures. Killing of specific target cells (open symbols) by effector cells and lack of killing of nonspecific targets (closed symbols) are shown. The ratio of effector to target cells is shown as the E:T ratio. Reproduced from ( ) with permission of the publisher.

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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Image of Figure 12.
Figure 12.

Protection of archaeosome-immunized mice against infection by the facultative intracellular bacterium, . BALB/c mice were vaccinated subcutaneously on days 0, 21, and 42 with 12.5 μg of a dipalmitoylated peptide entrapped in archaeosomes. After 3, 5, and 10 months, mice were challenged with live and the bacteria in spleens were enumerated 3 days later. C, mice not immunized; V, vaccinated mice. The number of spleens in each group of 5 mice that were still infected are shown as (/5). Modified from ( ) with permission of the publisher, with the exception of the 10-month data (J. W. Conlan, unpublished data).

Citation: Sprott G, Krishnan L. 2007. Archaeosome Vaccines, p 496-510. In Cavicchioli R (ed), Archaea. ASM Press, Washington, DC. doi: 10.1128/9781555815516.ch23
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