DEVELOPMENT OF RATIONALLY DESIGNED HCMV VACCINE STRAINS

描述：巨细胞病毒是一个主要的发病率和死亡率的来源， 免疫力低下的人。这种病毒导致了一系列 临床上明显的综合征，从威胁视力的视网膜炎， 艾滋病患者以骨髓和肾脏肺炎危及生命 同种异体移植受者。仅在美国，就有超过40亿人 美元的医疗保健费用是由于先天性 感染和疾病。我们的长期目标是创造一个安全和 有效的减毒活CMV疫苗， 疾病 我们用于产生减毒活CMV毒株的方法是基于 组合来自两个充分表征的CMV株的基因。基因从 CMV的Toledo株，一种强毒的野生型病毒，和Towne， 无毒的、适应细胞培养的病毒，在成人中不引起疾病， 可重组形成有效的减毒活病毒疫苗， 通过将重叠的互补链连接到允许的细胞中来获得候选物。 通过鉴定托莱多的致病基因， 将这些插入安全、无毒的汤恩基因组中，就可以产生一种菌株 其将赋予增加的免疫原性或复制， 汤恩这种新的CMV将被测试，以评估它是否保护 CMV疾病的患者。

DESCRIPTION: CMV is a major source of morbidity and mortality in immunocompromised individuals. This virus is responsible for a range of clinically apparent syndromes, ranging from sight-threatening retinitis in AIDS patients to life-threatening pneumonia in bone marrow and renal allograft transplant recipients. In the U.S. alone, over 4 billion dollars of health care costs are incurred as a consequence of congenital infection and disease. Our long term goal is to create a safe and efficacious live attenuated CMV vaccine that will confer protection from disease. Our approach for creating a live attenuated CMV strain is based on combining genes from two well characterized CMV strains. Genes from the Toledo strain of CMV, a virulent, wild-type virus, and Towne, an avirulent, cell culture adapted virus which causes no disease in adults, can be recombined to form effective live, attenuated virus vaccine candidates by cotransfecting overlapping cosmids into a permissive cell. By identifying genes in Toledo which contribute to its virulence and inserting these into the safe, avirulent Towne genome, a strain can be created which will confer an increased immunogenicity or replication to Towne. This new CMV will be tested to assess whether it protects recipients from CMV disease.