ATTENUATION OF THE NYCBH VACCINE STRAIN OF VACCINIA

NYCBH 牛痘疫苗株的减毒

• 批准号: 3506035
• 负责人: LENDON G PAYNE
• 金额: $ 22.46万
• 依托单位: APPLIED BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3506035
• 关键词: enzyme linked immunosorbent assay; gene expression; genetic manipulation; immunological substance; immunoregulation; laboratory mouse; molecular cloning; mutant; transcription termination; vaccinia virus; viral vaccines

The Phase I studies established the feasibility of using molecular approaches to derive from the NYCBH vaccine strain, stable attenuated mutants of unaltered immune efficacy. In this Phase II proposal selected mutants generated in the virulent NYCBH-IH isolate will be studied to determine their virulence parameters and immune protective capacity. An exhaustive study of virulence parameters in normal and immunocompromised mice will include, intracranial and intranasal LD50s, growth and dissemination from the site of inoculation, and the extent of pock formation on scarified skin. The immune protective capacity of mutants will be assessed by their ability to confer protection against a foreign pathogen by the expression of a single neutralizing antigen. The studies described above were performed for experimental convenience in a high virulence laboratory isolate of NYCBH. This information will be used to create specific mutations in a low virulence plaque purified isolate form the Wyeth vaccine seed stock (NYCBH-W) produced for the NIH under good manufacturing practice. The NYCBH-W mutants will be assessed for virulence parameters, and ability to confer protection against a foreign pathogen by the expression of a single neutralizing antigen. This data will be used to design first generation vaccine candidate(s) containing single mutations. Subsequently, combinations of mutations will be used to conform second generation vaccine candidate(s).

I期研究确定了使用分子的可行性 源于NYCBH疫苗菌株的方法，稳定减弱 未经改变的免疫疗效的突变体。 在此二期提案中选择 将研究在有毒的NYCBH-IH分离株中产生的突变体 确定其毒力参数和免疫保护能力。 一个 对正常和免疫功能低下的毒力参数的详尽研究 小鼠将包括颅内和鼻内LD50，生长和 与接种部位的传播和POCK的程度 在皮肤上形成。 突变体的免疫保护能力 将根据他们对外国提供保护的能力来评估 通过表达单个中和抗原的表达。 上述研究是为了实验方便的 NYCBH的高毒力实验室分离物。 这些信息将是 用于在低毒力斑块纯化中创建特定的突变 分离出为NIH生产的Wyeth疫苗种子库存（NYCBH-W） 在良好的制造实践下。 NYCBH-W突变体将进行评估 用于毒力参数，并具有针对A的保护 外国病原体通过单个中和抗原的表达。 这 数据将用于设计第一代疫苗候选者 包含单个突变。 随后，突变的组合将 被用来构造第二代疫苗候选者。