Immune stimulating activity was compared for lipid vesicles consisting of the total polar lipids of an archaeon Haloferax volcanii, and the eubacteria Planococcus spp. and Bacillus firmus. Each total polar lipid extract readily formed liposomes of similar size, within which the protein antigen ovalbumin was entrapped, with comparable loading and internalization. Subcutaneous immunization of mice resulted in anti-ovalbumin antibody titers for all adjuvants, with memory recall responses that were significantly greater with the archaeal lipid (H. volcanii versus Planococcus). More striking, induction of cytotoxic T cell activity against the entrapped antigen, measured 10 days following a single vaccination (primary response) rapidly declined by week 7 (secondary response after injections on days 0 and 21) in mice immunized with Planococcus spp. liposomes, but was sustained in mice immunized with H. volcanii archaeosomes. Surprisingly, antigen free-Planococcus liposomes evoked potent non-specific inflammatory cytokine production (IL-12 and IL-6) by dendritic cells whereas archaeal H. volcanii vesicles evoked little inflammatory cytokines. This suggested that overt inflammatory response might not necessarily aid sustenance of immunity. B. firmus liposomes consisted of phosphatidylglycerol, phosphatidylethanolamine and cardiolipin and was an ineffective CTL adjuvant, even for initiating a primary response. Considering that the polar lipids of H. volcanii and Planococcus spp. both consist of the same lipid classes (sulfoglycolipids, phosphoglycerols, and cardiolipins), the unique ability of archaeosomes to maintain antigen-specific T cell immunity may be attributable to a property of the archaeal 2,3-diphytanylglycerol lipid core.