DEVELOPMENT OF RECOMBINANT BCG-VP8 VACCINES

重组 BCG-VP8 疫苗的开发

• 批准号: 3790837
• 负责人: M GORZIGLIA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790837
• 关键词: Bacillus Calmette Guerin vaccine; Rotavirus; active immunization; antibody neutralization test; antiserum; antiviral antibody; attenuated microorganism; capsid; cross immunity; diarrhea; genetic manipulation; genetic strain; guinea pigs; immune tolerance /unresponsiveness; immunoprecipitation; laboratory mouse; monoclonal antibody; neutralizing antibody; protein structure; rotavirus vaccines; virus antigen; virus protein

Rotaviruses are major etiologic agents of severe diarrheal disease in infants and young children throughout the world. Neutralizing antibodies to rotaviruses have been shown to be induced independently by two outer capsid proteins, VP7 and VP4; these antibodies are associated with resistance to illness. The baculovirus expression system has been used to successfully express the VP4 of various rotavirus strains. The protein synthesized in this system exhibits native conformation based on its reactivity with polyclonal and available monoclonal antibodies (MAbs). In addition, guinea pigs immunized with such proteins developed antibodies that neutralized infectivity of the immunizing rotavirus efficiently. Moreover, immunization of guinea pigs with the expressed VP8 or VP5 cleavage subunit of VP4 induced antibodies that also neutralized rotavirus infectivity. Results obtained by cross- immunoprecipitation and by neutralization assay with these antisera suggest that the VP8 subunit of VP4 contains the major antigenic sites responsible for the neutralization of rotavirus via VP4. A major objective of this study was to characterize the VP4 protein of the murine rotavirus Eb strain (VP7 serotype 3 and define the mucosal immune response to this outer capsid protein in the homologous mouse model. We chose as a mucosal vector the human tuberculosis vaccine, bacille Calmette- Guerin (BCG), an attenuated strain of mycobacterium bovis that has been used extensively and safely in humans. BCG vaccine is commonly given at birth and elicits a long-lasting immune response with a single dose. It is also a highly effective adjuvant.

轮状病毒是严重腹泻病的主要病原体， 全世界的婴儿和幼儿。 中和抗体 轮状病毒的感染是由两个外部的 衣壳蛋白，VP 7和VP 4;这些抗体与 抵抗疾病。 杆状病毒表达系统已被用于成功表达 各种轮状病毒株的VP 4。 在这个系统中合成的蛋白质 基于其与多克隆的反应性显示天然构象， 可用的单克隆抗体（MAb）。 此外，免疫的豚鼠 用这种蛋白质开发的抗体， 有效免疫轮状病毒。 此外，豚鼠的免疫 用表达的VP 4诱导抗体的VP 8或VP 5切割亚基 也中和了轮状病毒的传染性。 结果通过交叉- 免疫沉淀和中和试验表明 VP 4的VP 8亚单位含有负责 用于通过VP 4中和轮状病毒。 本研究的一个主要目的是表征 鼠轮状病毒Eb株（VP 7血清型3和定义粘膜免疫 在同源小鼠模型中对这种外部衣壳蛋白的反应。 我们 选择人类结核病疫苗，卡介苗作为粘膜载体， Guerin（BCG），牛分枝杆菌的减毒菌株， 广泛且安全地用于人类。 卡介苗通常在 出生和elevant一个持久的免疫反应与单剂量。 是 也是一种高效佐剂。