Liposome adjuvants prepared from the total polar lipids ofHaloferax volcanii,Planococcusspp. andBacillus firmusdiffer in ability to elicit and sustain immune responses

Immune stimulating activity was compared for lipid vesicles consisting of the total polar lipids of an archaeonHaloferax volcanii, and the eubacteriaPlanococcusspp. andBacillus 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. volcaniiversusPlanococcus). 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 withPlanococcusspp. liposomes, but was sustained in mice immunized withH. volcaniiarchaeosomes. Surprisingly, antigen free-Planococcusliposomes evoked potent non-specific inflammatory cytokine production (IL-12 and IL-6) by dendritic cells whereas archaealH. volcaniivesicles evoked little inflammatory cytokines. This suggested that overt inflammatory response might not necessarily aid sustenance of immunity.B. firmusliposomes consisted of phosphatidylglycerol, phosphatidylethanolamine and cardiolipin and was an ineffective CTL adjuvant, even for initiating a primary response. Considering that the polar lipids ofH. volcaniiandPlanococcusspp. 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.