Interleukin-1 and interleukin-1 fragments as vaccine adjuvants.
The human interleukin-1beta (IL-1beta) 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-1beta nonapeptide reproduces the immunostimulatory and adjuvant effects of the whole mature IL-1beta, but does not possess any of the IL-1beta inflammatory, vasoactive, tumor-promoting, and systemically toxic effects, nor it can synergize with tumor necrosis factor alpha or 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.
Boraschi
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Dompé Research Center, L'Aquila, Italy. boraschi@dompe.it
Tagliabue
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D014612:Vaccines / Q000008:administration & dosage*; D019444:Vaccines, DNA / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007375:Interleukin-1; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014612:Vaccines; D019444:Vaccines, DNA