TOWARD SELECTIVE ELICITATION OF T(H)1-CONTROLLED VACCINATION RESPONSES - VACCINE APPLICATIONS OF BACTERIAL SURFACE-LAYER PROTEINS

Bacterial surface layer proteins have been utilized as combined vaccin e carrier/adjuvants and offer a number of advantages in these applicat ions. The crystalline protein arrays contain functional groups in prec isely defined orientations for coupling of haptens. Conventional appli cations of S-layer vaccines do not cause observable trauma or side eff ects. Depending on the nature of the S-layer preparations, antigenic c onjugates will induce immune responses of a predominantly cellular or predominantly humoral nature. Immune responses to S-layer-hapten conju gates are also observed following oral/nasal application. In the prese nt contribution, the status of investigations with S-layer conjugates in three main immunological projects is reviewed. In a project aimed a t immunotherapy of cancer, conjugates of S-layer with small, tumor-ass ociated oligosaccharides have been found to elicit hapten-specific DTH responses. An enlarged program of chemical synthesis has now been ini tiated to prepare a complete set of mucin-derived, tumor-associated ol igosaccharides and their chemically modified analogues for elicitation of cell-mediated immune responses to certain tumors in humans. In ano ther application, oligosaccharides derived from capsules of Streptococ cus pneumoniae type 8 have been linked to S-layer proteins and have be en found to elicit protective antibody responses in animals. Most rece ntly, allergen-S-layer conjugates have been prepared with the intentio n to suppress the T(H)2-directed, IgE-mediated allergic responses to B et nu 1, the major allergen of birch pollen. In the former two applica tions, the S-layer vaccine technology appears to offer the versatility needed to direct vaccination responses toward predominant control by T(H)1 or T(H)2 lymphocytes to meet the different therapeutic or prophy lactic requirements in each case. In the third application, work has p rogressed to a preliminary stage only.