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ISCOM(s)™ |
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Vaxjo ID |
7 |
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Vaccine Adjuvant Name |
ISCOM(s)™ |
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Alternative Names |
Immune stimulating complexes |
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Adjuvant VO ID |
VO_0000757
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Description |
Immune stimulating complexes (ISCOM@ adjuvant-Iscotec AB) ISCOM matrix is an open cage-like structure about 40 nm dia resulting from the interaction of saponins with cholesterol and phospholipid. Immunogenic ISCOMs are ISCOMs into which protein or other immunogenic molecules have been incorporated. They are used for veterinary vaccines and are being studied in various candidate vaccines in man in conjunction with defined saponin fractions (Cox and Coulter, 1997). |
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Stage of Development |
Clinical Trial |
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Components |
Two types of ISCOM particle or complex have been described in the literature. The first is the classic ISCOM, formed by the combination of cholesterol, saponin, phospholipid, and amphipathic proteins. The second is essentially the same structure but without the protein, and is usually referred to as Iscom Matrix (also called ISCOMATRIXy, a trademark of ISCOTEC AB). Typically, both ISCOMs and Iscom Matrix exist as spherical, hollow, rigid, cage-like particles of about 40 nm in diameter with a strong negative charge (Sjölander et al., 1998). |
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Structure |
ISCOMs are a complex composed of typically 0.5% Quillaja saponins, 0.1% cholesterol, 0.1% phospholipid, and antigen in phosphate-buffered saline (PBS). Occasionally, surfactants are used t are ISCOMs (such as Mega 10) but are removed from the final formulation before use (Vogel and Powell, 1995). |
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Molecular Weight |
A selection of c |
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Appearance |
ISCOMs form a clear product in solution (Vogel and Powell, 1995). |
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Storage |
Store ISCOMs at conditions compatible with the incorporated antigen(s). In general, storage in physiological buffers 4-8° C or may be stored at -70° C (Vogel and Powell, 1995). |
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Dosage |
Vaccines were administered intranasally to anaesthetised mice with an Eppendorf automatic pipette. The total dose volume was 12 μl, i.e. 6 μl per nostril. Mice were bled prior to a second dose of vaccine at 3 weeks post primary and again 1 week later (Coulter et al., 2003). |
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Function |
ISCOMs induce strong Thl and Th2 responses, good targeting and presentation, and excellent CTL responses. They are inexpensive, safe in animal studies and simple to formulate. It is important to incorporate immunogen into ISCOM for an effective CTL response (Cox and Coulter, 1997). |
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Safety |
The issue of toxicity with saponin-based adjuvants has been raised at various times as a potential impediment to their widespread use in human and veterinary vaccines. In mice and rats, crude saponins appear to only effect weight gain when administered orally but are toxic when administered parenterally. The LD50 for intravenously administered Quil A is 0.67 mg/kg in rats and doses of greater than 25 μg of Quil A given intraperitoneally can be toxic in the B6D2F1 strain of mice. Lethality in other strains of mice has also been reported with intraperitoneal or subcutaneous doses of ISCOMs containing from 10 to 50 μg of Quil A. When examined at autopsy, mice showed liver degeneration. Despite these findings with Quil A and Quil A-ISCOMs in rodents, there has been little toxicity observed with parenterally administered Quil A containing ISCOMs or QS-21 in larger animals such as chickens, cats, rhesus monkeys, dogs, sheep, cattle, or horses (Sjölander et al., 1998). |
| Related Vaccine(s) |
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| References |
Coulter et al., 2003: Coulter A, Harris R, Davis R, Drane D, Cox J, Ryan D, Sutton P, Rockman S, Pearse M. Intranasal vaccination with ISCOMATRIX adjuvanted influenza vaccine. Vaccine. 2003; 21(9-10); 946-949. [PubMed: 12547607].
Cox and Coulter, 1997: Cox JC, Coulter AR. Adjuvants--a classification and review of their modes of action. Vaccine. 1997; 15(3); 248-256. [PubMed: 9139482].
Sjölander et al., 1998: Sjölander A, Cox JC, Barr IG. ISCOMs: an adjuvant with multiple functions. Journal of leukocyte biology. 1998; 64(6); 713-723. [PubMed: 9850152].
Vogel and Powell, 1995: Vogel FR, Powell MF. A compendium of vaccine adjuvants and excipients. Pharmaceutical biotechnology. 1995; 6; 141-228. [PubMed: 7551218].
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