IMPROVED INFLUENZA A AND B VIRUS VACCINES

改进的甲型和乙型流感病毒疫苗

• 批准号: 2074130
• 负责人: SHENGQIANG LI
• 金额: $ 7.5万
• 依托单位: MEDIMMUNE VACCINES, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2074130
• 关键词: Orthomyxoviridae; chick embryo; complementary DNA; genetic library; influenza vaccines; influenzavirus A; method development; microorganism culture; microorganism immunology; recombinant DNA; recombinant proteins; recombinant virus; site directed mutagenesis; virus genetics; virus protein; virus replication

DESCRIPTION: (Adapted from the applicant's abstract) Improved replication of vaccine seed strains in embryonated hens' eggs would lower the cost of manufacturing inactivated influenza vaccines and allow more doses to be manufactured. Higher-growing influenza A and B vaccine donor viruses will be developed that can be genetically reassorted with poorly-growing fresh human isolates to generate master vaccine seed strains that are antigenically appropriate and grow well in embryonated eggs. The influenza matrix (M) gene is important for high virus replication in eggs, and may function in virion assembly by interacting with viral glycoprotein cytoplasmic tails. To generate higher-growing viruses, the investigators will use random mutagenesis of M genes of strains that grow well in eggs (A/PR/8/34 and B/Lee/40). A cDNA library of mutant M genes will be screened using the yeast two-hybrid system, Shengqiang to detect mutant M genes that exhibit an altered interaction with the cytoplasmic tail of the influenza hemagglutinin protein. Altered M genes selected by the two-hybrid screen will be introduced into infectious influenza viruses using reverse genetics technology. The resulting viruses will be evaluated for enhanced replication in eggs and their ability to perform as high-growing vaccine donor strains.

描述：（改编自申请人摘要）改进 在含胚鸡蛋中复制疫苗种子株将 降低灭活流感疫苗的生产成本， 生产更多的剂量。 高生长甲型和B型流感疫苗 供体病毒将被开发出来， 生长不良的新鲜人分离株，以生成主疫苗种子 抗原性合适且在胚胎中生长良好的菌株 鸡蛋 流感病毒基质（M）基因是高致病性病毒的重要基因， 在卵中复制，并且可以通过相互作用在病毒体组装中起作用。 带有病毒糖蛋白胞质尾。 以产生更高的增长 病毒，研究人员将使用随机诱变的M基因， 在卵中生长良好的菌株（A/PR/8/34和B/Lee/40）。 cdna文库 利用酵母双杂交系统筛选M基因突变体， Shengqiang检测显示改变相互作用的突变M基因 与流感血凝素蛋白质的胞质尾连接。改变 通过双杂交筛选选择的M基因将被导入到 利用反向遗传学技术研究传染性流感病毒。 的 将评估产生的病毒在鸡蛋中的增强复制， 它们作为高生长疫苗供体菌株的能力。