A structural comparison of the total polar lipids from the human archaea Methanobrevibacter smithii and Methanosphaera stadtmanae and its relevance to the adjuvant activities of their liposomes

Mice were immunized with bovine serum albumin (BSA) entrapped within archae osomes (i.e. liposomes) composed of the total polar lipids (TPL) from the t wo methanogenic archaea common to the human digestive tract. Methanobreviba cter smithii archaeosomes boosted serum anti-BSA antibody to titers compara ble to those achieved with Freund's adjuvant, whereas Methanosphaera stadtm anae archaeosomes were relatively poor adjuvants. An explanation for this d ifference was sought by analysis of the polar lipid composition of each arc haeobacterium. Fast atom bombardment mass spectrometry and NMR analyses of the purified lipids revealed a remarkable similarity in the ether lipid str uctures present in each TPL extract. However, the relative amounts of each lipid species varied dramatically. The phospholipid fraction in M. stadtman ae TPL was dominated by archaetidylinositol (50 mol% of TPL) and the glycol ipid fraction by beta-Glcp-(1,6)-beta-Glcp-(1,1)-archaeol (36 mol%), wherea s in M. smithii extracts, both caldarchaeol and archaeol lipids containing a phosphoserine head group were relatively abundant. Liposomes prepared fro m purified archaetidylinositol and from M. stadtmanae TPL supplemented with increasing amounts of phosphatidylserine elicited poor humoral responses t o encapsulated BSA. A dramatic loss in the adjuvanticity of M. smithii arch aeosomes was seen upon incorporation of 36 mol% of the uncharged lipid digl ucosyl archaeol and, to a lesser extent, of 50 mol% of archaetidylinositol. Interestingly, the relative rates of uptake of M. smithii and M. stadtmana e archaeosomes by phagocytic cultures in vitro were similar. Thus, the lipi d composition may influence archaeosome adjuvanticity, particularly a high diglucosyl archaeol and/or archaetidyl inositol content, resulting in a low adjuvant activity. (C) 1999 Published by Elsevier Science B.V. All rights reserved.