A Targeted Multiple Antigenic Peptide Vaccine Augments the Immune Response to Self TGF-β1 and Suppresses Ongoing Hepatic Fibrosis

Archivum Immunologiae Et Therapiae Experimentalis
Ya-Ping LiShuang-Suo Dang

Abstract

Transforming growth factor (TGF)-β1 expression is induced upon liver injury, and plays a critical role in hepatic fibrosis. Antibodies against TGF-β1 represent a novel approach in the treatment of hepatic fibrosis. However, TGF-β1 is not a suitable antigen due to immunological tolerance. In the current study, we synthesized a multiple antigenic peptide (MAP) vaccine against the dominant B-cell epitope of TGF-β1. The immunogenicity and potential therapeutic effects of this vaccine were examined using a rat model of hepatic fibrosis. Dominant B-cell epitopes of TGF-β1 were identified using bioinformatic program. An MAP vaccine corresponding to the 90-98 amino acid domain of TGF-β1 and containing four dendritic arms was synthesized using a 9-fluorenylmethoxycarbonyl solid phase method. Hepatic fibrosis which was induced in male Sprague-Dawley rats received a high-fat diet and ethanol (1.8 g/kg). Starting from the third week, rats were exposed to 40 % carbon tetrachloride (CCl4; 150 μl/100 g body weight twice weekly, initially 200 μl/100 g) treatment for a duration of 8 weeks. Rats received the MAP vaccine (100 μg) or Freund's adjuvant at weeks 1, 3, 5. A group of rats receiving the fibrosis-inducing regimen alone and a group of he...Continue Reading

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