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Adjuvant activity of 6-O-acyl-muramyldipeptides to enhance primary cellular and humoral immune responses in guinea pigs: adaptability to various vehicles and pyrogenicity.

Abstract
Thirteen 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamines (6-O-acyl-MDPs), including four inactive D-isoasparagine and L-isoglutamine analogs, were tested for their pyrogenicity and immunopotentiating activity to stimulate primary humoral and cellular immune responses in guinea pigs to a model protein antigen, ovalbumin, when administered in various vehicles. Among them, derivatives whose muramic acid residue was substituted by alpha-branched (and beta-hydroxylated) higher fatty acids at the carbon-6 position, especially 6-O-(2-tetradecylhexadecanoyl)-MDP (B3O-MDP) and, to a lesser extent, 6-O-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and its L-serine analog [BH48-MDP(L-Ser)], were found to exert strong adjuvant activity in both the induction of delayed-type hypersensitivity and the stimulation of circulating precipitating antibody levels when combined with nonirritating vehicles (liposomes, squalene-in-water emulsion, and phosphate-buffered saline). These vehicles did not efficiently support the adjuvant activity of MDP, the parent molecule of the above lipophilic derivatives. Pyrogenicity tests showed that introduction of alpha-branched higher fatty acid groups but not of straight, long-chain fatty acids at the 6-position of the muramic acid residue resulted in marked decrease of the pyrogenicity inherent to MDP via intravenous administration.
AuthorsM Tsujimoto, S Kotani, F Kinoshita, S Kanoh, T Shiba, S Kusumoto
JournalInfection and immunity (Infect Immun) Vol. 53 Issue 3 Pg. 511-6 (Sep 1986) ISSN: 0019-9567 [Print] UNITED STATES
PMID3744548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adjuvants, Immunologic
  • Emulsions
  • Liposomes
  • Pharmaceutical Vehicles
  • Acetylmuramyl-Alanyl-Isoglutamine
Topics
  • Acetylmuramyl-Alanyl-Isoglutamine (analogs & derivatives, pharmacology)
  • Adjuvants, Immunologic (pharmacology, toxicity)
  • Animals
  • Antibody Formation (drug effects)
  • Emulsions
  • Female
  • Fever (chemically induced)
  • Guinea Pigs
  • Immunity, Cellular (drug effects)
  • Liposomes (administration & dosage)
  • Pharmaceutical Vehicles
  • Rabbits
  • Structure-Activity Relationship

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