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Immune stimulating complexes (ISCOMs) are spherical open cage-like structures (typically 40 nm in diameter) that are spontaneously formed when mixing together
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
,
phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
and
Quillaja ''Quillaja'' is a genus of flowering plants, the only extant genus in the family Quillajaceae with two or three known species. It was once thought to be in the rose family, Rosaceae, but recent research shows it belongs in its own family. The i ...
saponins Saponins (Latin "sapon", soap + "-in", one of), also selectively referred to as triterpene glycosides, are bitter-tasting usually toxic plant-derived organic chemicals that have a foamy quality when agitated in water. They are widely distributed ...
under a specific
stoichiometry Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions. Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equal ...
. The complex displays immune stimulating properties and is thus mainly used as a
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesic ...
in order to induce a stronger immune response and longer protection.


History

ISCOM technology was invented in 1982 by Professor Bror Morein at the
Swedish University of Agricultural Sciences The Swedish University of Agricultural Sciences, or Swedish Agricultural University (Swedish: ''Sveriges lantbruksuniversitet'') (SLU) is a university in Sweden. Although its head office is located in Ultuna, Uppsala, the university has several c ...
in
Uppsala Uppsala (, or all ending in , ; archaically spelled ''Upsala'') is the county seat of Uppsala County and the List of urban areas in Sweden by population, fourth-largest city in Sweden, after Stockholm, Gothenburg, and Malmö. It had 177,074 inha ...
. The key components of ISCOMs are the
Quillaja ''Quillaja'' is a genus of flowering plants, the only extant genus in the family Quillajaceae with two or three known species. It was once thought to be in the rose family, Rosaceae, but recent research shows it belongs in its own family. The i ...
saponins Saponins (Latin "sapon", soap + "-in", one of), also selectively referred to as triterpene glycosides, are bitter-tasting usually toxic plant-derived organic chemicals that have a foamy quality when agitated in water. They are widely distributed ...
, which are derived from the bark of the Chilean soap-bark tree
Quillaja saponaria ''Quillaja saponaria'', the soap bark tree or soapbark, is an evergreen tree in the family Quillajaceae, native to warm temperate central Chile. In Chile it occurs from 32 to 40° South Latitude approximately and at up to 2000 m (6500&nbs ...
Molina. Quillaja saponins are well known for their ability to activate the immune system. It is also known that saponins in general can have toxic side-effects, including the induction of
haemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo ...
. However, when Quillaia saponins, cholesterol and phospholipids are mixed under the specific stoichiometry that forms ISCOMs, this haemolytic activity is practically eliminated, while the adjuvant activity is retained.


Immunological advantages

ISCOM-Matrix technology offers several
immunological Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...
and practical advantages over currently available
adjuvants In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy#Pharmacology, efficacy or Potency (pharmacology), potency of certain drugs. Specifically, the term can refer to: * Adju ...
. Most adjuvants on the market today mainly activate the humoral immune response (i.e. give an
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
response). There is, however, a clear need for adjuvants able to induce a cell-mediated immune response as well. ISCOM technology generally induces strong activation of both the cell-mediated ( Th1 response) and the humoral arms ( Th2 response) of the immune system. This generates all classes and sub-classes of
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, as well as potent cellular responses, e.g. cytotoxic T lymphocytes. This strong induction of the cellular response is one of the hallmarks of ISCOM-Matrix technology. A cell-mediated immune response is crucial for effective vaccination against intracellular pathogens and chronic infections. Moreover, the technology is highly efficient; its long-lasting immune responses allow reduction of the antigen dose. Typically, the dose can be decreased by a factor of 10 to 100, which will significantly cut the production cost of the vaccine. ISCOM-Matrix technology can also be of immense value in a situation when manufacturing capacity is inadequate in the face of an emerging threat such as an influenza pandemic. ISCOM technology is also able to induce an adaptive immune response in the presence of pre-existing antibodies, for example in new-borns who have maternal antibodies. The
chemical stability In chemistry, chemical stability is the thermodynamic stability of a chemical system. Thermodynamic stability occurs when a system is in its lowest energy state, or in chemical equilibrium with its environment. This may be a dynamic equilibri ...
of ISCOM-Matrix is of significant practical value. ISCOMs have demonstrated a shelf-life of several years during storage in aqueous solutions at +2-8°C (compared to months for free saponins). Since the ISCOM-Matrix is simply mixed with the antigen post-manufacturing, it offers great production advantages and flexibility in vaccine design. If required, however, the antigen can also be incorporated into the structure.


See also

*
Immunologic adjuvant In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word ''adiuvare'', meaning to help or aid. "An immunologic adjuvant is defined as any substance that ...
*
Immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
*
Immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...
*
Immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-sel ...
*
Inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading of disease, as in "self-inoculati ...
*
Virosomes A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane (either a mono- or bi-layer) vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells. Viruses are infectious ...
*
Vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
* Isconova *
Matrix-M Matrix-M adjuvant is a saponin-based adjuvant, which stimulates humoral and cellular immune responses to vaccines. It was patented in 2020 by Novavax. It is composed of nanoparticles from saponins extracted from '' Quillaja saponaria'' (soapba ...


References


Further reading

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External links


Isconova's homepage
{{Webarchive, url=https://web.archive.org/web/20090403072421/http://www.isconova.se/ , date=2009-04-03 Immunology Adjuvants