Oral administration of genetically modified Bifidobacterium displaying HCV-NS3 multi-epitope fusion protein could induce an HCV-NS3-specific systemic immune response in mice

口服转基因双歧杆菌,展示 HCV-NS3 多表位融合蛋白,可在小鼠体内诱发 HCV-NS3 特异性全身免疫反应

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作者:Saki Takei, Chika Omoto, Koichi Kitagawa, Naoya Morishita, Takane Katayama, Katsumi Shigemura, Masato Fujisawa, Masato Kawabata, Hak Hotta, Toshiro Shirakawa

Abstract

More than 170 million people worldwide are chronic HCV (Hepatitis C virus) carriers, and about 30% of them will develop progressive liver disease, such as cirrhosis and hepatocellular carcinoma. A combination of pegylated interferon-α with ribavirin, the standard treatment for HCV infection, has been effective in fewer than 50% of patients infected with HCV genotype 1. A strong T cell response against the nonstructural protein 3 (NS3) is important for recovery from acute HCV infection, and an early multi-specific CD4+ helper and CD8+ cytotoxic T cell response is critical for HCV clearance. In the present study, we successfully constructed a genetically modified Bifidobacterium longum (B. longum) displaying recombinant HCV-NS3 peptides containing some CD4 and CD8 epitopes located in the HCV-NS3 region as an oral vaccine against chronic HCV infection. The oral administration of this vaccine could induce NS3-specific immune responses in mice through intestinal mucosal immunity. Our findings suggest that this novel oral vaccine has great potential as a novel oral vaccine against chronic HCV infection.

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