Using poly-N-acetyl glucosamine gel matrix to deliver IL-12 with anti-schistosomasis vaccination

Mohamed L. Salem, Wael Y. Attia, Yousry E. Al-Bolkiny, Ismail M. Al-Sharkawi, Marina Demcheva, John Vournakis

Research output: Contribution to journalJournal articlepeer-review

6 Scopus citations

Abstract

Background: Interleukin (IL)-12 is a potential adjuvant in a variety of diseases including schistosomiasis. The clinical use of IL-12, however, is limited by the toxicity associated with its systemic administration. We have developed a novel delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of sustaining the release of proteins (e.g. interleukins) and adjuvant effects. The main aim of this study was to use a mouse model to test whether IL-12 released from F2 gel can induce adjuvant effects in the schistosomiasis setting as compared to those obtained after systemic delivery of IL-12. Methodology: First, we compared the toxicity induced by paracrine (delivered by F2 gel) and systemic IL-12. Second, we compared the induction of cytokines induced by paracrine and systemic IL-12. Third, we compared the adjuvant effects of paracrine and systemic IL-12-based prophylactic vaccination against schistosomiasis using soluble worm antigen preparation (SWAP). Results: IL-12 released from F2 gel did not induce significant toxicity measured by alanine aminotransferase (ALT). We found similar serum levels of IFN-γ, TNF-α and IL-2 after paracrine and systemic IL-12 treatments. We also found that vaccination with F2 gel/SWAP/IL-12 induced higher anti-schistosomal effects than IL-12/SWAP as evidenced by 1) the decrease in the total liver egg counts; 2) the reduction in the granuloma size and fibrotic reaction in the liver; and 3) the amelioration of the liver functions. Conclusion: Collectively, these results indicate that IL-12-F2 gel delivery approach could be considered as a potential strategy for the treatment of schistosomiasis.

Original languageEnglish
Pages (from-to)318-328
Number of pages11
JournalJournal of Infection in Developing Countries
Volume4
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • Cytokines
  • IL-12
  • Paracrine treatment
  • Schistosoma mansoni
  • SWAP
  • Systemic treatment
  • Vaccination

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