Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses

Abstract

We describe here a novel type of immunostimulating complex, called 'iscom', in which virus membrane proteins are presented in a multimeric form. The matrix of the iscom is the glycoside Quil A (Spikoside; Iscotec AB), extracted from the bark of Quillaja saponaria Molina, which forms micelles at the critical micellar concentration of 0.03%. In micelle form, Quil A probably has regions accessible for hydrophobic interaction with the membrane proteins so that it can form complexes with them. Iscoms have been prepared with membrane proteins of para-influenza-3 (PI-3), measles and rabies viruses, and their immunizing potency tested in animals. In these experiments, iscoms prove to be at least 10 times more potent than micelles formed by aggregation of the membrane proteins alone. Iscoms of PI-3 and measles viruses also stimulate the formation of antibody to the fusion (F) protein, which is considered to be poorly immunogenic. No side effects of iscoms or of protein micelles have been observed.

The iscom structure as an immune-enhancing moiety: experience with viral systems

“…Most currently used vaccines against rabies virus are inactivated viruses which are used for pre-and postexposure treatment of rabies infection. Rabies virus iscoms prepared from whole purified virus were among the first iscoms described (Morein et al, 1984). In vitro experiments showed that human CD4+ T-cell clones could be stimulated with these iscoms.…”

“…Iscom was first described in 1984 (Morein et al, 1984). It is a cage-like structure, usually about 30 to 40 nm in diameter, composed of glycosides present in the adjuvant Quil-A, cholesterol, the immunizing (protein) antigen and also, in most cases, phospholipids.…”

Development of Vaccine Adjuvants: A Historical Perspective

“…A second lipid-based particle with extensive application is the ISCOM/ISCOMATRIX system, based on Quillaja saponin, cholesterol, and phospholipids. Dissolution of these components in the presence of the detergent Mega 10 followed by removal of the detergent by dialysis results in a 30-to 40-nm cagelike structure [245] which will incorporate amphiphilic antigens to produce the original immune-stimulating complex (ISCOM) structure [246]. This structure is an active producer of antibody but is set apart from most of the adjuvant systems developed thus far in that it effectively delivers antigen to the MHC class I pathway [247], although not by the TAP (peptide transporter) pathway.…”

Adjuvants for a New Generation of Vaccines

“…One approach has been the production of rscoMs which were originally described by Morein et al (31) as particles consisting of quil A and membrane proteins. The preparation of rscoMs allowed reduction in the quil A concentration required for adjuvant effects.…”