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 provide a physically optimal presentation of antigen to the immune system. An iscom particle without incorporated antigen is called the iscom matrix, or just matrix, and can be used as a conventional adjuvant that is added to the antigen whose immunogenicity is to be reinforced. The 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 triterpenoids can be used as a crude preparation of Quillaja saponins or as purified preparations of Quillaja triterpenoids. The various triterpenoids have different characteristics, of which some are relevant to vaccine development such as the iscom-forming capacity, the immunomodulatory capacity, a low cell lytic property and low toxicity in general. Consequently, various compositions of triterpenoids, including efficient nontoxic adjuvant formulations or inert carrier formulations, can be made. The currently used iscom vaccine and experimental vaccines induce a broad immune response, including major histocompatibility complex (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. producing interleukin (IL)-2 and interferon-gamma and favouring cell-mediated immunity. A T(H)2-like response may also be evoked, with cells producing IL-4 and IL-10 and promoting humoral immunity. However, the same 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 candidate for induction of mucosal immunity. Iscoms containing different kinds of antigens in various experimental vaccines evoke secretory IgA or cytotoxic T cell responses when administered orally and intranasally. Experimental iscom vaccine formulations have been shown to induce protective immunity to a number of micro-organisms, including viruses and retroviruses, parasites and bacteria, in several species, including primates.