The immune stimulating complex (
ISCOM) is a 40 nm nanoparticle used as a delivery system for
vaccine antigens, targeting the immune system both after parenteral and
mucosal administration. The
ISCOM is made up of
saponin,
lipids and
antigen usually held together by hydrophobic interaction between these three components. The compulsory elements to form the
ISCOM structure are
cholesterol and
saponin. When the
antigen is omitted the
ISCOM-MATRIX is formed. There are a number of
saponins that can form
ISCOMs, and many other substances (including
antigens, targeting and immuno-modulating molecules) can be incorporated into the
ISCOM provided they are hydrophobic or rendered to be hydrophobic. Thus, it is possible to create
ISCOM particles with different properties. After parenteral immunisation of the
ISCOM, the T cell response is first detected in the draining lymph node. Subsequently, the T cell response is localised to the spleen, while the B cell response is first found both in the draining lymph nodes and in the spleen. Up to 50 days later, the majority of the antibody producing cells is found in the bone marrow (BM). In contrast,
antigens that have been adjuvanted in an oil
emulsion, limit the T cell response to the draining lymph nodes while the B cell response is found in the draining lymph nodes and spleen, but not in the BM. The
ISCOM efficiently evokes CD8+, MHC class 1 restricted T cell response. The deposit of
antigens both to the endosomal vesicles and to the cytosol of antigen presenting cells (APCs) explains why both T helper cells (vesicles) and cytotoxic T lymphocytes (cytosol) are efficiently induced by
ISCOMs. The T helper (Th) cell response is balanced in the sense that both Th1 and Th2 cells are induced. Prominent
IL-12 production by cells in the innate system is a characteristic reaction induced by
ISCOMs, promoting the development of a strong Th1 response. After
mucosal administration by the intranasal or the intestinal routes, the
ISCOM induces strong specific mucosal
IgA responses in local and remote mucosal surfaces. Also T cell responses are evoked by the
mucosal administration. A large number of experimental
ISCOM vaccines have been tested and protection has been induced against a number of pathogens in various species including chronic and
persistent infections exemplified by human immune deficiency virus 1 (HIV-1), and 2 (HIV-2) and simian immune deficiency virus (SIV) in primates, and various herpes
virus infections in several species. In contrast to a conventional rabies virus
vaccine the
ISCOM rabies formulation protected mice after exposure to the virulent virus. Recently, experimental
ISCOM vaccines were shown to efficiently induce immune response in newborns of murine and bovine species in the presence of maternal
antibodies, while conventional
vaccines have failed.
ISCOM vaccines are on the market for horses and cattle and several other
ISCOM vaccines are under development. Since the
ISCOM and the
ISCOM-MATRIX can be blended with live
attenuated vaccine antigens without hampering the proliferation of the live
vaccine antigens, it opens the possibility to use the
ISCOM adjuvant system in a mixture of live and
killed vaccine antigens.