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

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.

Changes in Liver Cell Apoptosis after Vaccination by Schistosomulae Antigen and/or Artesunat Treatment in Murine Schistosoma Mansoni

“…Regarding SLAP plus IL12 vaccine, it gave better results than artesunate 3 weeks post infection in the present study with reductions reaching 67.6% in worm burden ,88.7% in mean number of eggs in liver, and 88.8% in mean number of eggs in intestine. This is in agreement with Salem et al [50] who stated that IL12 is a potential adjuvant in many diseases including schistosomiasis.IL-12 increase the cell mediated immunity and Th1 cell response [17]. In another study, Feng et al [51] reported that the worm and egg reduction rates were 64.3% and 79.9% in mice vaccinated by S. japonicum DNA with IL12.…”

Localized Interleukin-12 for Cancer Immunotherapy

“…A polysaccharide gel matrix, designated F2 gel, is comprised of 70% deacetylated poly-N-acetyl glucosamine (p-GlcNAc) coformulated with lactate salt. p-GlcNAc gels were evaluated as slow-release cytokine depots for GM-CSF, IL-2, and IL-12 (356)(357)(358)(359)(360). In particular, i.t.…”

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

“…Natural polymers include proteins like albumin, and polysaccharides like chitosan and poly-N-acetyl glucosamine. [400][401][402] Natural polypeptides possess high biocompatibility but require robust identification, standardization, and purification methods to reduce potential batch-to-batch variation. Polymers derived from natural sources can also be immunogenic, which hinders their performance.…”