Enhancement of serum antibody production in mice by oral administration of lipophilic derivatives of muramyl peptides and bacterial lipopolysaccharides with bovine serum albumin.

Lipophilic derivatives of muramyl peptides, namely N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys (L18)] and 6-O-(2-tetradecylhexadecanoyl) -MDP (B30-MDP) were demonstrated to significantly enhance anti-bovine serum albumin (BSA) antibody production when they were incorporated in liposomes with BSA and administered by gastric intubation to BALB/c mice on days 0 and 1 (the primary immunization) and on days 27 and 28 (booster). N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) itself showed negligible activity under the same experimental conditions. A stearoyl derivative of sodium beta-N-acetylglucosaminyl-(1-4)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl (D)-meso-diaminopimelic acid-(D)-amide-D-alanine (GM-53) that was isolated by enzymatic degradation of L. plantarum cell wall peptidoglycans also showed a powerful adjuvant effect by oral administration in liposomes with BSA. Similar or stronger adjuvant effects were observed by oral administration of bacterial lipopolysaccharide (LPS) preparations, KO3 LPS isolated from K. pneumoniae (a noncapsulated mutant, LEN-1), Bacto lipopolysaccharide W derived from. E. coli (O127:B8) and BIOSTIM F1 fraction derived from K. pneumoniae (O1:K2) Liposomes as a vehicle for oral administration were not always required for the manifestation of the adjuvant effects of MDP-Lys (L18) and BIOSTIM F1. These compounds, but not B30-MDP, showed a powerful adjuvant effect when orally administered with BSA in phosphate buffered saline.