Interleukin-1 and Interleukin-1 Fragments as Vaccine Adjuvants

The human interleukin-1 (IL-1) 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-1 nonapeptide reproduces the immunostimulatory and adjuvant effects of the whole mature IL-1, but does not possess any of the IL-1 inflammatory, vasoactive, tumor-promoting, and systemically toxic effects, nor it can synergize with tumor necrosis factor ALPHAor other molecules in inducing toxicity and shock. The IL-1BETA 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-1BETA 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.