TEMPERATURE-SENSITIVE VACCINE STRAINS OF S ENTERITIDIS

肠炎沙门氏菌温度敏感疫苗株

• 批准号: 3436680
• 负责人: ANNE MORRIS-HOOKE
• 金额: $ 6.88万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1990-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3436680
• 关键词: Salmonella food poisoning; Salmonella infections; Salmonella vaccines; active immunization; antibacterial antibody; bacterial genetics; bactericidal immunity; chickens; communicable disease control; disease /disorder model; enzyme linked immunosorbent assay; gene expression; genetic markers; genetic recombination; genetic strain; immunological substance; linkage mapping; live vaccine; microorganism culture; microorganism immunology; surface antigens; temperature sensitive mutant; virulence

The ultimate goal of this proposed research is the development of a live vaccine for the prevention of Salmonella infection of and subsequent shedding from poultry, in order to reduce the reservoir of infection for man. Single temperature-sensitive mutants of a chicken-virulent strain of Salmonella enteritidis will be isolated, using standard methods of mutagenesis and enrichment, and characterized with respect to phenotype at the body temperature of chickens, reversion frequency, linkage of the ts mutations to selectable chromosomal markers. The single ts strains will also be evaluated for immunogenic potential in a model of oral immunization and challenge in chickens. Strains of S. enteritidis containing multiple mutations of identical temperature-sensitive phenotype, utilizing the linkage of the ts lesions to the selectable markers, will then be constructed. Such strains will contain all the surface antigens in their natural conformation, but will be incapable of sustained replication in the vaccinee. Their reversion frequency will be reduced to negligible levels (-10-21) ensuring their safety, both for the vaccinee and susceptible contacts of the vaccinee. Oral administration of the vaccine strains should induce the formation of specific mucosal antibodies, preventing colonization and, therefore, disease and sustained shedding. The three ts mutations, once characterized and present in a "master" strain, would be suitable for incorporation into other appropriate S. enteritidis strains for the construction of vaccines to prevent Salmonella disease in a variety of animal and human systems.

这项拟议研究的最终目标是发展 预防沙门氏菌感染的活疫苗和 随后从家禽脱落，以减少水库 人类感染。 a的单个温度敏感突变体 鸡肉肠菌株的肠道肠道菌株将被孤立 使用诱变和富集的标准方法，以及 在体温下在表型方面的特征 鸡的复归频率，TS突变与 可选的染色体标记。 单个TS菌株也将 在口服模型中评估免疫原性 鸡的免疫和挑战。 S. enteritidis的菌株 包含相同温度敏感的多个突变 表型，利用TS病变与可选的TS 然后，将构建标记。 这样的应变将包含全部 其自然构象中的表面抗原，但会 疫苗无法持续复制。 他们的 恢复频率将降低至可忽略的水平（-10-21） 确保其安全性，包括疫苗和易感性 疫苗的接触。 疫苗的口服给药 菌株应诱导特定粘膜的形成 抗体，防止定殖，因此，疾病和 持续的脱落。 曾经表征的三个TS突变 并出现在“主”菌株中，适合 纳入其他适当的S. entitidis菌株 建造疫苗以防止沙门氏菌疾病 动物和人类系统的多样性。