IMMUNOSTIMULATING COMPLEXES - CLINICAL POTENTIAL IN VACCINE DEVELOPMENT

An immunostimulating complex (iscom) is a particle containing several copies of an antigen, with a built-in adjuvant. It is constructed to p rovide a physically optimal presentation of antigen to the immune syst em. An iscom particle without incorporated antigen is called the iscom matrix, or just matrix, and can be used as a conventional adjuvant th at is added to the antigen whose immunogenicity is to be reinforced. T he unique components of the iscom matrix are saponins (triterpenoids) from the tree Quillaja saponaria, which exhibit a unique affinity for cholesterol and thereby facilitate the stability of the complex. The t riterpenoids can be used as a crude preparation of Quillaja saponins o r as purified preparations of Quillaja triterpenoids. The various trit erpenoids have different characteristics, of which some are relevant t o vaccine development such as the iscom-forming capacity, the immunomo dulatory capacity, a low cell lytic property and low toxicity in gener al. Consequently, various compositions of triterpenoids, including eff icient nontoxic adjuvant formulations or inert carrier formulations, c an be made. The currently used iscom vaccine and experimental vaccines induce a broad immune response, including major histocompatibility co mplex (MHC) class I and II T cell responses. The MHC class II response encompasses a prominent response of T helper 1 (T(H)1)-like cells. pr oducing interleukin (IL)-2 and interferon-gamma and favouring cell-med iated immunity. A T(H)2-like response may also be evoked, with cells p roducing IL-4 and IL-10 and promoting humoral immunity. However, the s ame influenza virus envelope antigen in a micellar nonadjuvanted form induces a more prominent T(H)2 type of response, with cells producing more IL-10. The iscom particle is also an interesting nonreplicating c andidate for induction of mucosal immunity. Iscoms containing differen t kinds of antigens in various experimental vaccines evoke secretory I gA or cytotoxic T cell responses when administered orally and intranas ally. Experimental iscom vaccine formulations have been shown to induc e protective immunity to a number of micro-organisms, including viruse s and retroviruses, parasites and bacteria, in several species, includ ing primates.