ISCOMs

Apart from liposomes, other vehicles for delivery of antigens to the immune system, such as iscoms, emulsions, and micellar structures, are presently under investigation (Jiskoot et al., 1986b Allison and Byars, 1986 Kersten et al., 1988a,b). 

Kersten, G. F. A., Van de Put, A., Teerlink, T., Beuvery, E. C., and Crommelin, D. J. A. (1988a). Immunogenicity of liposomes and iscoms containing the major outer membrane protein of Neisseria gonorrhoeae -Influence of protein content and liposomal bilayer composition. Inf. Immun., 56. 1661-1664. 

IP4 Inositol tetrakisphosphate IPF Idiopathic pulmonary fibrosis IPO Intestinal peroxidase IpOCOCq Isopropylidene OCOCq I/R Ischaemia-reperfusion IRAP IL-1 receptor antagonist protein IRF-1 Interferon regulatory factor 1 la Short-circuit current ISCOM Immune-stimulating complexes... 

In addition to the immunostimulatory substances discussed above, the adjuvanticity of a variety of other substances is also being appraised. These include saponins, liposomes and ISCOMs. 

ISCOMs are stable (non-covalent) complexes composed of a mixture of Quil A, cholesterol and (an amphipathic) antigen. ISCOMs stimulate both humoral and cellular immune responses and have been used in the production of some veterinary vaccines. Their use in humans, however, has not been licensed so far, mainly due to safety concerns relating to the Quil A component. 

Morein, B., M. Villacres-Eriksson, and K. Lovgren-Bengtsson, Iscom, a delivery system for parenteral and mucosal vaccination. Dev Biol Stand, 1998. 92 33-9. 

Kersten, G.E, and D.I Crommelin, Liposomes and ISCOMS as vaccine formulations. Biochim Biophys Acta, 1995. 1241(2) 117-38. 

Adjuvants can be classified into two main groups based on their mechanism of action. The first group are particulate materials that act as vaccine delivery systems and target associated antigens into APC. These include emulsions, microparticles, iscoms, and liposomes. The second group are immunostimula-tory and are derived mainly from pathogens. These include lipopolysaccharide... 

Mineral Salts Immunostimulatory adjuvants Lipid particles Particulate adjuvants Mucosal adjuvants Aluminium hydroxide, aluminium phosphate, calcium phosphate Saponins (e.g., QS21), MDP derivatives, bacterial DNA (CpG oligos), LPS, MPL and synthetic derivatives, lipopeptides, cytokines (e.g., GM-CSF, IL-2, IL-12) Liposomes, virosomes, iscoms, cochleates, emulsions (e.g., Freunds adjuvant, SAF, MF59 ) Poloxamer particles, virus-like particles, PLG microparticles Cholera toxin (CT), mutant toxin (e.g., LTK63, LTR72), heat labile enterotoxin (LT), microparticles, polymerized liposomes, chitosan... 

ISCOMs (immune Influenza subunit Protective immunity to challenge 222... 

Lovgren, K., Kaberg, H., and Morein, B. (1990), An experimental influenza subunit vaccine (iscom) Induction of protective immunity to challenge infection in mice after intranasal or subcutaneous administration, Clin. Exp. Immunol., S2,435-439. 

Hsu, S. C., Schadeck, E. B., Delmas, A., Shaw, M., and Steward, M. W. (1996), Linkage of a fusion peptide to a CTL epitope from the nucleoprotein of measles virus enables incorporation into ISCOMS and induction of CTL responses following intranasal immunization, Vaccine, 14,1159-1166. 

Carol, H., Nieto, A., Villacres-Eriksson, M., and Morein, B. (1997), Intranasal immunization of mice with Echinococcus granulosus surface antigens iscoms evokes a strong immune response, biased towards glucidic epitopes, Parasite Immunol., 19,197-205. 

Hu, K. F., Elvander, M., Merza, M., Akerblom, L., BrAndenburg, A., and Morein, B. (1998), The immunostimulatory complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses, Clin. Exp. Immunol., 113, 235-243. 

Crouch CE, Daly J, Herrly W, Hairirairt D, Wilkiirs J, Fraircis MJ (2005) Tire use of a systemic piime/mucosal boost sti ategy witlr air equiire influenza ISCOM vaccine to induce protective immunity in horses. Vet Immuirol Immuiropatlrol 108 345—355. 

Iscoms (Immune-stimulating complexes) are stable complexes of cholesterol, phospholipid, and Quil A (derived from Quillaja saponaria) in size ranges from 40 to lOOnm. They are promising carriers for antigens in subunit vaccines. Iscoms are considered to be multi-micellar structures, shaped and stabilized by hydro-phobic interactions, electrostatic repulsion, steric factors and possibly hydrogen bonds. Protection... 

Kersten, G.F.A. Aspects of Iscoms. Stuctural, Pharmaceutical and Adjuvant Properties. Ph.D. thesis. University of Utrecht, 1990 93-104. 

Many compounds can act as adjuvants. Their classification is made difficult by the variety in chemical composition and the overlapping, often poorly understood, mechanisms of action. Only aluminum adjuvants are approved by the FDA for use in human vaccines. Quil A is a saponin that is commonly used as an adjuvant in veterinary vaccines and is also a component of immune-stimulating complexes (ISCOM). These adjuvants are addressed in some detail below. A detailed discussion of other types of adjuvants can be found in recent books and reviews on this subject. 

Aluminium salts are currently the only widely used adjuvants in human vaccines (65). Developments in the understanding of the structure, composition, and preparation of immunostimulating complexes (ISCOMs) have been reviewed and compared. 

Sjolander A, Cox JC, Barr IG. ISCOMs an adjuvant with multiple functions. J Leukoc Biol 1998 64(6) 713-23. 

Bungener L, Huckriede A, Wilschut J, Daemen T (2002) Delivery of protein antigens to the immune system by fusion-active virosomes A comparison with liposomes and ISCOMs. Biosci Rep 22 323-338... 

Barr IG, Sjolander A, Cox JC (1998) ISCOMs and Other Saponin Based Adjuvants. Adv Drug Deli Reviews 32 247... 

Emulsions (e.g., Freund s, SAF, MF59), liposomes, iscoms, virosomes, lipopeptide... 

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