Interleukin-1 and interleukin-1 fragments as vaccine adjuvants

The human interleukin-1b (IL-1b) domain in position 163-171, comprising the amino acids VQGEESNDK, has been synthesized as a nine-amino-acid-long peptide and used in vivo as a nontoxic HCl salt. The IL-1b nonapeptide reproduces the immunostimulatory and adjuvant effects of the whole mature IL-1 beta, but does not possess any of the IL-1 beta inflammatory, vasoactive, tumor-promoting, and systemically toxic effects, nor it can synergize with tumor' necrosis factor a or other molecules in inducing toxicity and shock. The IL-1b fragment is active as adjuvant either when administered together with the antigen or if inoculated separately; it can be physically linked to the antigen or used as a discrete peptide. Moreover, the DNA sequence encoding the IL-1b domain has been included in an experimental DNA vaccine with positive results. Thus, immunostimulatory sequences can be identified within a pleiotropic cytokine like IL-1 and used in the rational design of novel vaccination strategies. (C) 1999 Academic Press.