Study On The Antigenicity Of The HCV HVR1 Peptides

Hepatitis C virus (HCV) is the major cause of, non-A non-B viral hepatitis .More than half of 180 million people infected with HCV will become chronic and develop cirrhosis and perhaps hepatocellular carcinoma . No effective treatment and vaccine can prevent the infection because the pathogenic mechanism of progression of hepatitis caused by HCV has not yet been clearly elucidated. The variability of HVR1 to escape immune supervilline is the main cause of HCV persistence. It is reported that important neutralizing epitopes that can induce neutralizing antibody are in HVR1 of HCV. Seven HVR1 antigen peptides are designed and synthesized according to the analysis of sequence diversity of HCV HVR1 in Chinese patients infected with genotype lI/lb and IIJ/2a HCV and the character of protein antigen. Strong antigenicity has been showed in the peptide of number five , two ,three and four by lymphocytes transformation test. In spite of the negative results in control , the lymphocyte proliferation clones in sample group were seen under light microscope. By calculating the stimulate index (SI) PBMC(peripheral blood mononuclear cell) could be stimulated by four synthetic peptides evidently. Among these peptides , PBMC of 36.17% patients infected with HCV could be induced proliferative reaction by the fifth peptide ,34.04% to the second5peptide,27.66% to the third peptide,21.28% to the fourth peptide,12.77% to the first peptide ,8.5% to the sixth peptide,2.13% to the seventh peptide, PBMC of 63.83% patients (30 cases) of the sample group could be induced proliferative reaction by these peptides. Strong antigenicity have been verified in the number two, five, three and four synthetic peptide by the computer modeling .Strong antigenicity has been showed in the sera of immuned mice by number two, three and four peptide by ELISA .Cross-activity is existing between the second peptide and the three other peptides. The results of the three methods are almost same . Strong antigenicity is existing in the above synthetic peptides .The regularity of the lymphocyte epitopes in HCVHVR1 have been found initially .The AA 384 389, 389 400, 395 403 may be the antigeh epitopes of HCVHVR1. Especially , the AA 384 389 in the N-terminus has not been reported.Strong foundation has been built to the study of the neutralizing epitopes of HVR1 and multi-peptide vaccine to HCV.