摘要：今年全球首次出現低致病性禽流感病毒H7N9 經基因重組而成新病毒的人病例，致重症的病程急速惡化與死亡率偏高，而病例無禽接觸史比率也漸升，加上臺灣首例境外移入病例的H7N9 病毒有克流感的抗藥性，及病毒蛋白顯現提昇人傳染力的胺基酸突變，因此研展快速檢驗與治療所需抗體及疫苗對臺灣防疫迫切重要。為維護國人健康，本整合計畫凝集具成功研發H6N1 單株抗體經驗與專利、流感病毒及公共衛生專家，期能協同合作完成因應新型H7N9 流感之準備。子計畫間的合作目標與預期成果有六：(1)以Baculovirus 表現及量產自人分離H7N9 病毒的重組蛋白和類病毒顆粒；(2) 搭配病毒胺基酸序列突變區之peptide，建立具特異性和廣效性之鼠源單株抗體；(3)完成單株抗體之量產、純化與結合力分析；協助研發H7N9 檢測試劑與疫苗；(4)以病毒蛋白與單株抗體進行血清流行病學研究，探究高風險群的H7N9血清抗體盛行率，評估其公共衛生衝擊；(5)探討重複的季節流感疫苗接種是否能產生較廣的H7N9 交叉血球凝集抑制抗體或中和抗體，而有較高的交叉保護與較少的類流感病癥；及(6)早期偵測H7N9 之無症狀人傳人，提供以科學數據為基準的防疫策略。深信此群體計畫可鑑定出對H7N9 專一性高中和能力或對其他亞型交叉反應的抗原決定基，有助於未來病毒檢測與疫苗研發。
Abstract: H7N9, a low pathogenic avian influenza virus (AIV), has led to mostly asymptomatic infections in avian species. However, severe and fatal human cases of the newly reasserted novel H7N9 viruses have continuously occurred since the first reporting in March, 2013. Public health preparedness must be initiated after risk assessment based on recent findings, including increasing percentages of those cases without contact history of birds, the appearance of Tamiflu drug-resistant H7N9 virus strains (involving the first imported Taiwan case from mainland China), the cumulative evidence of the isolated human H7N9 viruses possessing amino acid residues with aerosol transmissibility, and fast disease progression. Therefore, it is very important to develop rapid laboratory diagnostics, antibodies and vaccines for better pandemic preparedness. To assure public health in Taiwan, we proposed this multi-disciplinary integrated research program project by inviting team members of those with a successful experience in developing H6N1 monoclonal antibody (mAb), patent number 10221483400, and strong backgrounds in influenza virus and public health. Through close collaboration, we intended to achieve the following six specific aims in response to the health threat of novel H7N9: 1) expression and high-yield production of H7N9 viral recombinant proteins and viral-like particles using baculovirus system; 2) matching with the synthetic peptides containing the mutated amino acid residues of viral proteins, our mouse mAb libraries with both high specific neutralizing activities and broad cross-reactions will be generated; 3) finishing the high-yield production, purification and binding affinity assays of these mAbs, and develop the H7N9 diagnostic kits and potentially potent vaccines; 4) conducting a seroepidemiological study to measure the seroprevalence rates of H7N9 antibodies in different high risk human populations, by using viral proteins and mAbs developed by other team members; 5) investigating whether the annual repeated vaccinations for preventing from seasonal influenza infection could produce more broadly neutralizing/hemagglutinating inhibition antibodies (Nt/HI Abs) and cross-reactive antibodies for inhibiting H7N9 so that these vaccines would have higher cross-protection and less frequencies of flu-like symptoms; and 6) early detection of H7N9 human-to-human transmission with no apparent signs of illness for evidence-based public health policies. We certainly believe that this proposed integrated project and team effort will not only identify H7N9-specific highly neutralizing epitopes and cross-reactive epitopes for different subtypes of AIVs, but also provide fully support for developing H7N9 laboratory diagnostic kits, potentially potent vaccines and establishing related standard operating procedures (SOPs) for better public health planning and implementing the most effective prevention/control strategies for H7N9.
H7N9 Influenza Virus: Viral Recombinant Protein
Taiwan Prevention Strategies