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Related Experiment Videos

Engineering human IL-18 with increased bioactivity and bioavailability.

Bethany Swencki-Underwood1, Mark R Cunningham, George A Heavner

  • 1Centocor Inc., Biopharmaceutical Research, 145 King of Prussia Road, Radnor, PA 19087, USA. bswenck2@cntus.jnj.com

Cytokine
|June 6, 2006
PubMed
Summary
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Interleukin-18 (IL-18) can enhance DNA vaccine immune responses. Researchers developed and tested IL-18 variants, finding one (V11I/T63A) with improved bioactivity and expression for potential use as a vaccine adjuvant.

Area of Science:

  • Immunology
  • Molecular Biology
  • Vaccinology

Background:

  • Cytokines, such as interleukin-18 (IL-18), can function as adjuvants in DNA vaccines, boosting immune responses to encoded antigens.
  • IL-18 has demonstrated adjuvant properties with specific DNA vaccine formulations.

Purpose of the Study:

  • To optimize interleukin-18 (IL-18) for enhanced efficacy as a DNA vaccine adjuvant.
  • To identify IL-18 variants with improved receptor binding and bioactivity through computational modeling and experimental validation.

Main Methods:

  • Developed a computational model for IL-18/IL-18 receptor (IL-18R) binding to predict beneficial IL-18 variants.
  • Engineered and expressed IL-18 variants linked to a secretion signal sequence in mammalian cells.
  • Assessed bioactivity of secreted IL-18 variants by measuring interferon gamma (IFNgamma) induction in peripheral blood mononuclear cells (PBMCs) and IL-18R binding via BIAcore analysis.

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  • Evaluated inhibition of IL-18 variants by IL-18 binding protein (IL-18BP).
  • Main Results:

    • Secreted IL-18 variants exhibited bioactivity, inducing IFNgamma production in PBMCs and binding to IL-18R.
    • IL-18 variants were susceptible to inhibition by IL-18BP, as shown by neutralization assays.
    • One variant, V11I/T63A, demonstrated significantly enhanced bioactivity and improved expression in mammalian cells compared to native IL-18.

    Conclusions:

    • The engineered IL-18 variant V11I/T63A shows promise as a DNA vaccine adjuvant due to increased bioactivity and expression.
    • This optimized IL-18 variant could potentially lead to more effective DNA vaccine formulations.
    • Further research into this variant could advance the development of novel vaccine strategies.