ISCOM
Encyclopedia
ISCOM
Immune stimulating complexes (ISCOMs) are spherical open cage-like structures (typically 40 nm in diameter) that are spontaneously formed when mixing together cholesterol
, phospholipids and Quillaia saponins under a specific stoichiometry
. The complex displays immune stimulating properties and is thus mainly used as a vaccine
adjuvant
in order to induce a stronger immune response and longer protection.
in Uppsala
. The key components of ISCOMs are the Quillaja
saponins, which are derived from the bark of the Chilean soap-bark tree Quillaia saporinaria Molina. Quillaia 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. However, when Quillaia saponins, cholesterol and phospholipids are mixed together under the specific stoichiometry that forms ISCOMs, this haemolytic activity is practically eliminated, while the adjuvant activity is retained.
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, 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
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.
Immune stimulating complexes (ISCOMs) are spherical open cage-like structures (typically 40 nm in diameter) that are spontaneously formed when mixing together cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, phospholipids and Quillaia saponins under a specific stoichiometry
Stoichiometry
Stoichiometry is a branch of chemistry that deals with the relative quantities of reactants and products in chemical reactions. In a balanced chemical reaction, the relations among quantities of reactants and products typically form a ratio of whole numbers...
. The complex displays immune stimulating properties and is thus mainly used as a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
in order to induce a stronger immune response and longer protection.
Content
ISCOM technology was invented in 1982 by Professor Bror Morein at the Swedish University of Agricultural SciencesSwedish University of Agricultural Sciences
The Swedish University of Agricultural Sciences or Sveriges Lantbruksuniversitet is a university in Sweden. Although its head office is located in Ultuna, Uppsala, the university has several campuses in different parts of Sweden, the other main facilities being Alnarp in Lomma Municipality, Skara,...
in Uppsala
Uppsala
- Economy :Today Uppsala is well established in medical research and recognized for its leading position in biotechnology.*Abbott Medical Optics *GE Healthcare*Pfizer *Phadia, an offshoot of Pharmacia*Fresenius*Q-Med...
. The key components of ISCOMs are the Quillaja
Quillaja
Quillaja is a genus of flowering plants, the only genus in the family Quillajaceae. It was once thought to be in the rose family, Rosaceae, but recent research shows it belongs in its own family. The inner bark of the soap bark tree contains saponin, which is a natural soap. Members of this...
saponins, which are derived from the bark of the Chilean soap-bark tree Quillaia saporinaria Molina. Quillaia 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. However, when Quillaia saponins, cholesterol and phospholipids are mixed together 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 and practical advantages over currently available adjuvants. Most adjuvants on the market today mainly activate the humoral immune response (i.e. give an antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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, 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
Chemical stability
Chemical stability when used in the technical sense in chemistry, means thermodynamic stability of a chemical system.Thermodynamic stability occurs when a system is in its lowest energy state, or chemical equilibrium with its environment. This may be a dynamic equilibrium, where individual atoms...
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.