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SAFETY OF ARCHAEOSOME ADJUVANTS EVALUATED IN A MOUSE MODEL*

G. B. Patel, Abdelwahab Omri, L. Deschatelets, G. Dennis Sprott
Published 2002 · Medicine, Chemistry

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ABSTRACT Archaeosomes, liposomes prepared from the polar ether lipids extracted from Archaea, demonstrate great potential as immunomodulating carriers of soluble antigens, promoting humoral and cell mediated immunity in the vaccinated host. The safety of unilamellar archaeosomes prepared from the total polar lipids (TPL) of Halobacterium salinarum, Methanobrevibacter smithii or Thermoplasma acidophilum was evaluated in female BALB/c mice using ovalbumin (OVA) as the model antigen. Groups of 6–8 mice were injected (0.1 mL final volume) subcutaneously at 0 and 21 days, with phosphate buffered saline (PBS), 11 µg OVA in PBS, 1.25 mg of antigen-free archaeosomes in PBS (ca 70 mg/kg body wt), or PBS containing 11–20 µg OVA encapsulated in 1.25 mg archaeosomes. Animals were monitored daily for injection site reactions, body weight, temperature and clinical signs of adverse reactions. Sera were collected on days 1, 2, 22, and 39 for analyses of creatine phosphokinase. Mice were sacrificed on 39 d, sera were collected for biochemical analyses, and major organs (liver, spleen, kidneys, heart, lungs) were weighed and examined macroscopically. There were no indications of adverse reactions or toxicity associated with any of the archaeosome adjuvants. None of the antigen-free archaeosomes elicited significant anti lipid antibodies when subcutaneously injected (1 mg each at 0, 1, 2, and 4 weeks) in mice, although anti H. salinarum lipid antibodies were detected. These anti lipid antibodies cross-reacted with the TPL of T. acidophilum archaeosomes but not with the TPL of M. smithii archaeosomes nor with lipids of ester liposomes made from l-α-dimyristoylphosphatidylcholine (DMPC), l-α-dimyristoylphosphatidylglycerol (DMPG), and cholesterol (CHOL). In vitro hemolysis assay on mouse erythrocytes indicated no lysis with M. smithii or T. acidophilum archaeosomes at up to 2.5 mg/mL concentration. At this concentration, H. salinarum archaeosomes and DMPC/DMPG/CHOL ester liposomes caused about 2% and 4% hemolysis, respectively. Based on this mouse model evaluation, archaeosomes are well-tolerated and appear relatively safe for potential vaccine applications.
This paper references
10.1128/JB.184.2.556-563.2002
Complete polar lipid composition of Thermoplasma acidophilum HO-62 determined by high-performance liquid chromatography with evaporative light-scattering detection.
H. Shimada (2002)
10.1139/O90-007
Antibodies to liposomal phosphatidylcholine and phosphatidylsulfocholine.
N. Wassef (1990)
Archaeosomes Induce LongTerm CD8þ Cytotoxic T Cell Response to Entrapped Soluble Protein by the Exogenous Cytosolic Pathway, in the Absence of CD4þ
L. Krishnan (2000)
10.1016/0005-2736(86)90068-4
Cytolytic activity of liposomes containing stearylamine.
E. Yoshihara (1986)
10.1016/S1389-0344(01)00101-0
Recent developments in adjuvants for vaccines against infectious diseases.
D. O'hagan (2001)
10.1007/978-1-4757-0283-5_22
Recommendations for the Assessment of Adjuvants (Immunopotentiators)
D. Stewart-Tull (1989)
Preparation of Liposomes. In Liposomes: A Practical Approach; New, R.R.C., Ed.
R.R.C. New (1990)
10.1016/0041-008X(74)90202-6
The parenteral toxicity of clindamycin 2-phosphate in laboratory animals.
J. Gray (1974)
Tolerability of Liposomes In Vivo
G. Storm (1993)
Cytokine-containing liposomes as vaccine adjuvants.
L. Lachman (1996)
10.1080/0738-859991229170
Archaeobacterial ether lipid liposomes (archaeosomes) as novel vaccine and drug delivery systems.
Patel Gb (1999)
10.4049/jimmunol.166.3.1885
The Potent Adjuvant Activity of Archaeosomes Correlates to the Recruitment and Activation of Macrophages and Dendritic Cells In Vivo1
L. Krishnan (2001)
10.1016/S0005-2760(96)00163-4
Identification of β-l-gulose as the sugar moiety of the main polar lipid of Thermoplasma acidophilum
M. Swain (1997)
Archaeosomes as Immunomodulating Carriers for Acellular Vaccines to Induce Cytotoxic T Lymphocyte (CTL) Responses and Protect the Vaccinated Host Against Intracellular Pathogens and Cancer
G. D. Sprott (2001)
10.1016/0264-410X(95)00105-A
Adjuvant activity of non-toxic Quillaja saponaria Molina components for use in ISCOM matrix.
B. Rönnberg (1995)
Archaebacterial lipids: structure, biosynthesis and function.
M. Kates (1992)
10.1016/S0264-410X(02)00091-9
2nd meeting on novel adjuvants currently in/close to human clinical testing. World Health Organization-Organization Mondiale de la Santé Fondation Mérieux, Annecy, France, 5-7 June 2000.
R. Kenney (2002)
10.1016/0165-2478(94)90179-1
The immunodominant peptide from listeriolysin in Quil A liposomes vaccinates CD8+ cytolytic T cells and confers protection to infection.
G. Lipford (1994)
10.4049/jimmunol.165.9.5177
Archaeosomes Induce Long-Term CD8+ Cytotoxic T Cell Response to Entrapped Soluble Protein by the Exogenous Cytosolic Pathway, in the Absence of CD4+ T Cell Help1
L. Krishnan (2000)
10.1515/cclm.1986.24.1.11
Catalytic Enzyme Activity Concentration in Plasma of Man, Sheep, Dog, Cat, Rabbit, Guinea Pig, Rat and Mouse. Approach to a Quantitative Diagnostic Enzymology. I. Communication
J. Lindena (1986)
10.1016/0264-410X(93)90190-9
Adjuvants--a balance between toxicity and adjuvanticity.
R. Gupta (1993)
Archaeobacterial ether lipid liposomes (archaeosomes) as novel vaccine and drug delivery systems.
G. B. Patel (1999)
10.1128/IAI.68.1.54-63.2000
Archaeosome Vaccine Adjuvants Induce Strong Humoral, Cell-Mediated, and Memory Responses: Comparison to Conventional Liposomes and Alum
L. Krishnan (2000)
Production of antibodies against phosphocholine, phosphatidylcholine, sphingomyelin, and lipid A by injection of liposomes containing lipid A.
B. G. Schuster (1979)
10.3109/08982109509039918
Toxicity and Biodistribution of Liposomes of the Main Phospholipid from the Archaebacterium Thermoplasma Acidophilum in Mice
H. Freisleben (1995)
10.1016/S0264-410X(01)00041-X
Immunization of mice with lipopeptide antigens encapsulated in novel liposomes prepared from the polar lipids of various Archaeobacteria elicits rapid and prolonged specific protective immunity against infection with the facultative intracellular pathogen, Listeria monocytogenes.
J. Conlan (2001)
10.1007/978-1-4899-2516-9_1
Glyco-, Phosphoglyco- and Sulfoglycoglycerolipids of Bacteria
M. Kates (1990)
10.1007/BF00902745
Stability of pressure-extruded liposomes made from archaeobacterial ether lipids
C. Choquet (2004)
10.1016/0003-2697(84)90782-6
A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids.
D. Wessel (1984)
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc
R. Edelman (1990)
2nd Meeting on Novel Adjuvants Currently in/Close to Human Clinical Testing, World Health Organization, France, 5–7 June
R. T. Kenney (2000)
10.1016/0264-410X(87)90105-8
Adjuvant formulation for use in vaccines to elicit both cell-mediated and humoral immunity.
N. Byars (1987)
The Clinical Chemistry of Laboratory Animals
P. Menzies (1989)
10.1016/S0264-410X(96)00292-7
Haemolytic activities of plant saponins and adjuvants. Effect of Periandra mediterranea saponin on the humoral response to the FML antigen of Leishmania donovani.
W. R. Santos (1997)
10.1016/0009-3084(93)90070-J
Toxicity screening of liposomes.
M. Parnham (1993)
10.1128/IAI.66.6.2859-2865.1998
Liposomes Containing Lipid A Serve as an Adjuvant for Induction of Antibody and Cytotoxic T-Cell Responses against RTS,S Malaria Antigen
Roberta L. Richards (1998)
Purification of Ether Lipids and Liposome Formation from Polar Lipid Extracts of Methanogenic Archaea
G. D. Sprott (1995)
10.1111/J.1574-6968.1997.TB12618.X
Archaeosomes as novel antigen delivery systems.
G. Sprott (1997)



This paper is referenced by
10.1007/978-1-4020-5041-1_1
Bioactive Entrapment and Targeting Using Nanocarrier Technologies: An Introduction
M. Mozafari (2006)
10.1093/glycob/cwn038
Adjuvant potential of archaeal synthetic glycolipid mimetics critically depends on the glyco head group structure.
G. Sprott (2008)
10.1002/9783527632909.CH16
New Nanobiotechnological Strategies for the Development of Vectors for Cancer Vaccines
S. Geary (2012)
10.1080/10915810802352703
Safety of Intranasally Administered Archaeal Lipid Mucosal Vaccine Adjuvant and Delivery (AMVAD) Vaccine in Mice
G. B. Patel (2008)
PHARMACEUTICALLY ENGINEERED NANOPARTICLES FOR ENHANCING IMMUNE RESPONSES TO HIV-1 TAT AND GAG p24 PROTEINS
Jigna D. Patel (2006)
10.1016/j.vaccine.2008.02.026
Archaeosome adjuvants: immunological capabilities and mechanism(s) of action.
L. Krishnan (2008)
10.1016/j.arcmed.2015.06.004
Reality of a Vaccine in the Prevention and Treatment of Atherosclerosis.
V. García-González (2015)
10.1016/j.jbiotec.2014.09.015
Archaeosomes can efficiently deliver different types of cargo into epithelial cells grown in vitro.
A. B. Zavec (2014)
10.1080/10611860410001670044
Archaeosomes as Self-adjuvanting Delivery Systems for Cancer Vaccines*
L. Krishnan (2003)
10.1533/9781908818683.219
Lipids and inorganic nanoparticles in oral insulin delivery
T. A. Sonia (2015)
Formulation And Characterization Of Various Drug Carrier Systems And Investigating Their Ability For Solubilization Of Poorly Water Soluble Drugs
I. Ullah (2013)
10.1007/s11095-010-0241-4
Nanoparticle Delivery Systems in Cancer Vaccines
Yogita Krishnamachari (2010)
10.1128/9781555815813.CH8
Membrane Adaptations of (Hyper)Thermophiles to High Temperatures
A. Driessen (2007)
10.1038/NPG.ELS.0004316
Archaeal Membrane Lipids
G. B. Patel (2006)
10.1007/978-1-4020-5041-1_2
Archaeosomes as Drug and Vaccine Nanodelivery Systems
G. B. Patel (2006)
10.1080/08982104.2017.1376683
In vitro evaluation of archaeosome vehicles for transdermal vaccine delivery
Y. Jia (2018)
10.1081/LPR-200039200
Archaeosomes as Adjuvants for Combination Vaccines
G. B. Patel (2004)
Liposomal β-Glucan: Preparation, Characterization and Anticancer Activities
Majed Halwani (2015)
10.33552/ann.2020.06.000639
Niosome Encapsulated Bromelain Reduced IL-6 and TNF-α in LPS Induced in Mice
Siavash Hosseinpour Chermahini (2020)
10.1038/nri1728
Immunization without needles
S. Mitragotri (2005)
10.1586/14760584.3.3.307
Vaccines against Francisella tularensis – past, present and future
W. Conlan (2004)
10.1002/9780470015902.A0000385.PUB3
Archaeal Membrane Lipids and Applications
G. Sprott (2011)
10.1016/j.ijpharm.2018.07.041
Recent advancements in oral administration of insulin‐loaded liposomal drug delivery systems for diabetes mellitus
Chun Y Wong (2018)
10.4049/jimmunol.173.1.566
Phosphatidylserine Receptor-Mediated Recognition of Archaeosome Adjuvant Promotes Endocytosis and MHC Class I Cross-Presentation of the Entrapped Antigen by Phagosome-to-Cytosol Transport and Classical Processing1
K. Gurnani (2004)
10.1007/978-981-10-3647-7_3
Nanotechnology-Based Immunotherapeutic Strategies for the Treatment of Cancer
Rajeev Sharma (2017)
Archaeosomes induce enhanced cytotoxic T lymphocyte responses to entrapped soluble protein in the absence of interleukin 12 and protect against tumor challenge.
L. Krishnan (2003)
10.1016/j.vaccine.2011.05.015
Archaeosomes with encapsulated antigens for oral vaccine delivery.
Z. Li (2011)
Classical Processing by Phagosome-to-Cytosol Transport and Cross-Presentation of the Entrapped Antigen Promotes Endocytosis and MHC Class I Recognition of Archaeosome Adjuvant Phosphatidylserine Receptor-Mediated
J. Kennedy (2004)
10.1002/9781118394144.CH5
Features and Applications of Halophilic Archaea
X. Abrevaya (2012)
10.1016/J.VACCINE.2007.09.042
Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-adjuvanted vaccines.
G. B. Patel (2007)
10.1208/s12249-019-1293-3
Lipid-Based Nanocarriers for Lymphatic Transportation
Nikhar Vishwakarma (2019)
10.1016/j.toxlet.2011.03.001
Progress in understanding adjuvant immunotoxicity mechanisms.
A. Batista-Duharte (2011)
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