Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identifica...Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1(HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte(CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin(HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.展开更多
AIM： To develop the epitope-based vaccines to prevent Hepatitis C virus （HCV）/Hepatitis B virus （HBV） infections. METHODS： The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD （residuals aa2-21） and C2 VKFPGGGQIVGGVY...AIM： To develop the epitope-based vaccines to prevent Hepatitis C virus （HCV）/Hepatitis B virus （HBV） infections. METHODS： The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD （residuals aa2-21） and C2 VKFPGGGQIVGGVYLLPRR （residuals aa22-40）, envelope epitope E GHRMAWDMMMNWSP （residuals aa315-328） and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC （residuals aa124-147） were displayed in five different sites of the flock house virus capsid protein as a vector, and expressed in E. coli cells （pET-3 system）. Immunoreactivity of the epitopes with anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B patients were determined. RESULTS： The expressed chimedc protein carrying the HCV epitopes C1, C2, E （two times）, L3C1-I2E-L1C2- L2E could react with anti-HCV antibodies. The expressed chimeric protein carrying the HBV epitopes S, I3S could react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with anti- HCV and anti-HBs antibodies. CONCLUSION： These epitopes have highly specific and sensitive immunoreaction and are useful in the development of epitope-based vaccines.展开更多
基金supported by Razi Vaccine & Serum Research Institute, Karaj, Iran
文摘Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1(HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte(CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin(HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.
基金Supported by the Yunnan Province Natural Science Foundation,No. 2003C0076M
文摘AIM： To develop the epitope-based vaccines to prevent Hepatitis C virus （HCV）/Hepatitis B virus （HBV） infections. METHODS： The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD （residuals aa2-21） and C2 VKFPGGGQIVGGVYLLPRR （residuals aa22-40）, envelope epitope E GHRMAWDMMMNWSP （residuals aa315-328） and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC （residuals aa124-147） were displayed in five different sites of the flock house virus capsid protein as a vector, and expressed in E. coli cells （pET-3 system）. Immunoreactivity of the epitopes with anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B patients were determined. RESULTS： The expressed chimedc protein carrying the HCV epitopes C1, C2, E （two times）, L3C1-I2E-L1C2- L2E could react with anti-HCV antibodies. The expressed chimeric protein carrying the HBV epitopes S, I3S could react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with anti- HCV and anti-HBs antibodies. CONCLUSION： These epitopes have highly specific and sensitive immunoreaction and are useful in the development of epitope-based vaccines.
