CYTOKINES AS VACCINE ADJUVANTS - INTERLEUKIN-1 AND ITS SYNTHETIC PEPTIDE 163-171

The possibility of preventing infectious diseases by employing efficacious vaccine is rapidly growing as a consequence of the new technologies in recombinant DNA and protein chemistry. However, the increasing number of synthetic and recombinant antigens further stresses the role of appropriate adjuvants to ensure maximal vaccine activity and the protection of all vaccinees. Several approaches can be applied to develop safe and effective agents capable of enhancing specific immune responses which can then protect the host from the pathogen. Among others, the direct use as adjuvant of those cytokines which are induced in animals by the classical Freund's adjuvants has recently become a matter of investigation. In particular, interleukin 1 (IL-1) has been shown to possess adjuvant activity for a variety of infectious and tumour antigens. However, the numerous side effects associated with the proinflammatory action of IL-1 represent a serious disadvantage for its use as a vaccine adjuvant. It was therefore of great interest that a nonpeptide contained in the IL-1beta sequence (residues 163-171 corresponding to the sequence VQGEESNDK) is devoid of all proinflammatory activities but maintains the immunostimulating activity of the whole IL-1beta. Thus, peptide 163-171 was successfully employed in animals to potentiate the specific immune response against T-helper-dependent cellular antigens, T helper-independent polysaccharidic antigens and recombinant as well as synthetic antigenic preparations derived from human pathogens. Furthermore, IL-1 and peptide 163-171 have been successfully used in tumour vaccines in experimental systems. It can therefore be concluded that peptide 163-171 is potentially a good candidate as vaccine adjuvant for human use.