BOVINE PARAINFLUENZA 3 VIRUS AS A NOVEL VACCINE VECTOR

牛副流感 3 病毒作为新型疫苗载体

基本信息

批准号：
6017911
负责人：
AURELIA A HALLER
金额：
$ 9.98万
依托单位：
MEDIMMUNE VACCINES, INC.
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-15 至 2000-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6017911
关键词：
Paramyxovirus biotechnology genetic manipulation hamsters laboratory mouse parainfluenza virus type 1 parainfluenza virus type 2 respiratory syncytial virus technology /technique development transfection /expression vector vaccine development vector vaccine virus protein

项目摘要

Bovine parainfluenza type 3 virus (bPIV3) was shown in clinical trials to be safe when administered to small infants and children, and attenuated, causing no lower respiratory disease in children. bPIV3 was genetically stable after replication in children. These three characteristics provide the basis for the use of bPIV3 as an effective vector vehicle to deliver foreign antigens. Recently, an infectious cDNA of bPIV3 was engineered at Aviron that permits the isolation of recombinant viruses by reverse genetics. This Phase I SBIR proposal will demonstrate the feasibility of this approach by introducing the surface glycoproteins of human parainfluenza virus types l, 2 and 3 (hPIV1, 2, 3) and human respiratory syncytial virus (hRSV) (subgroups A and B) into the genetic genome of bPIV3. Both, hPIV and hRSV. are the causes of upper and lower respiratory disease in infants, children, and immunocompromised or elderly adults, resulting not only in significant numbers of hospitalizations but also in morbidity. No vaccine is currently available for either PIV or RSV associated disease and subunit approaches have so far failed. A Phase II SBIR grant will be used to complete preclinical testing in a subhuman primate model and to initiate human clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The ultimate product of these studies are live attenuated human parainfluenza virus (types l, 2 and 3) and human respiratory syncytial virus (subgroups A and B) vaccines using bovine parainfluenza virus 3 as a vector.

临床试验表明，牛副流感 3 型病毒 (bPIV3) 对小婴儿和儿童给药是安全的，并且会减毒，不会引起儿童下呼吸道疾病。 bPIV3 在儿童体内复制后遗传稳定。这三个特征为使用 bPIV3 作为有效的载体来递送外源抗原提供了基础。最近，Aviron 设计了 bPIV3 的感染性 cDNA，允许通过反向遗传学分离重组病毒。该 I 期 SBIR 提案将通过将人副流感病毒 1、2 和 3 型 (hPIV1、2、3) 和人呼吸道合胞病毒 (hRSV)（A 亚型和 B 亚型）的表面糖蛋白引入到bPIV3 的遗传基因组。 hPIV 和 hRSV 两者。是导致婴儿、儿童、免疫功能低下或老年人上呼吸道和下呼吸道疾病的原因，不仅导致大量住院患者，而且导致发病率。目前还没有针对 PIV 或 RSV 相关疾病的疫苗，并且亚单位方法迄今已失败。 II 期 SBIR 拨款将用于完成非人类灵长类动物模型的临床前测试并启动人体临床试验。拟议的商业应用：这些研究的最终产品是使用牛副流感病毒3作为载体的减毒活人副流感病毒（1型、2型和3型）和人呼吸道合胞病毒（A和B亚型）疫苗。