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


METHODS
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-gamma, TNF-alpha 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.


CONCLUSIONS
Collectively, these results indicate that IL-12-F2 gel delivery approach could be considered as a potential strategy for the treatment of schistosomiasis.
Salem
Mohamed Labib
ML
Medical University of South Carolina, Charleston, SC, USA. mohamedlabibsalem@yahoo.com
Attia
Wael Y
WY
Al-Bolkiny
Yousry E
YE
Al-Sharkawi
Ismail M
IM
Demcheva
Marina
M
Vournakis
John
J
D000117:Acetylglucosamine / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000097:blood; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D018664:Interleukin-12 / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000517:prevention & control; D014611:Vaccination
D016207:Cytokines; D005782:Gels; C113831:poly-N-acetyl glucosamine; D018664:Interleukin-12; D000117:Acetylglucosamine