Mycobacterial adjuvants

When crude endotoxin from the heptose-less mutant of Salmonella typhimurium is combined with trehalose dimycolate from mycobacteria in oil droplets and injected directly into established tumors (line 10 hepatocellular carcinoma) in syngeneic guinea pigs, rapid regression of the tumors occurs and over 90% of the animals are cured. The three required components for activity in this tumor model are (a) the endotoxin (b) the mycobacterial adjuvant, trehalose dimycolate and (c) a compound satisfying the minimal structural requirement (muramyl dipeptide) for adjuvant activity by bacterial cell wall materials. The mycobacterial cell wall skeleton is able to replace the latter two components. 

Au°, while aurothiomalate suppressed only the development of mycobacterial adjuvant. The Au° preparation was approximately 1000 times more potent than aurothiomalate (per gold content). 

Grandia, A.A., Devisser, H., Vanembden, J.D.A., Vanderzee, R., Vanderberg, W.B., Hazenberg, M.P. (1991). Natural antibodies to 65 kD mycobacterial heat shock protein in rats do not correlate with susceptibility for mycobacterium-tuberculosis induced adjuvant arthritis. Immunobiology 182, 127-134. 

Freund s incomplete adjuvant (FIA) is a similar product. It differs from FCA in that it lacks the mycobacterial component and, consequently, displays somewhat lesser adjuvanticity. The mode of action of FIA is largely attributed to depot formation. The mycobacterial components in FCA have additional direct immunostimulatory activities. Although it is one of the most potent adjuvant substances known, FCA is too toxic for human use. 

Adipex-P phentermine. acyuvant peptide (muramyl dipeptide MDP) is a Af-acetylmuramyl dipeptide, identified as the minimum structural constituent of the mycobacterial cell wall component of Freund s complete adjuvant, which is necessary for adjuvant activity. It and many of its analogues have been investigated as adjuvants in the immunization of animals, as (immunostimulant) immunomodulators. It also has some pyrogenic activity. 

Freund s adjuvant (mycobacterial cells in a water-in-oil emulsion containing the antigen in the water phase) (75) is used for stimulating the production of antibodies against the antigen used. A five to ten fold titer of antibodies is obtained with complete Freund s adjuvant in comparison with incomplete adjuvant lacking Mycobacteria. It also induces delayed hypersensitivity to the antigen (9, 72). 

Fig. 2. Simplified scheme of the mycobacterial cell wall and its adjuvant active derivatives Wax D, WSA, MDP [quoted from (40)]...

Migliore, D., and P. Jolles A hydrosoluble adjuvant active mycobacterial poly-saccharide-peptidoglycan . Preparation by a simple extraction technique of the bacterial cells (strain Peurois). FEBS Letters 25, 301 (1972). 

Azuma, I., K. SuGiMURA, T. Taniyama, M. Yamawaki, Y. Yamamura, S. Kusumoto, S. Okada, and T. Shiba Adjuvant activity of mycobacterial fractions immunological properties of synthetic N-acetyl-muramyl dipeptide and the related compounds. Infect. Immun. 14, 18 (1976). 

Shibata Y., Honda I., Justice J. P. et al. 2001. Thl adjuvant A-acetyl-D-glucosamine polymer up-regulates Thl immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice. Infect Immun 69 6123-6130. 

C19H32N4O11 492.482 Identified as the minimum structural constit. of the mycobacterial cell wall component of Freund s complete adjuvant which is necessary for adjuvant activity. 

Freund s (1947, 1956) complete adjuvant is the most popular adjuvant. It consists of killed and dried mycobacterial cells suspended in an emulsifying oil. 

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