Safety of archaeosome adjuvants evaluated in a mouse model

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Journal titleJournal Of Liposome Research
Pages353372; # of pages: 20
SubjectArchaeosome adjuvants; Archaeal lipid liposomes; Mouse model; Safety
AbstractArchaeosomes, 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.
Publication date
AffiliationNational Research Council Canada; NRC Institute for Biological Sciences
Peer reviewedNo
NRC numberPATEL2002A
NPARC number9376974
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Record identifier1024922f-98ee-4391-9779-e1c6c89ad70a
Record created2009-07-10
Record modified2016-05-09
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