RECOMBINANT AVIRULENT SALMONELLA VACCINES AGAINST TB

结核病仍然是最重要的全球健康问题之一。 今天，就像几个世纪以来一样。虽然……的发展 治疗结核病的化疗药物导致了戏剧性的 20世纪50年代S以来结核病发病率的下降 20世纪80年代的S，特别是在发达国家，这种病还没有出现 在全世界范围内都得到了控制并在不断增加。大约1个 世界上三分之一的人口感染了分枝杆菌 结核病，每年有300万人死于结核病。 控制感染性疾病的化疗替代方法 疾病一直是针对特定成分的疫苗的发展 病原体或病原体产生的毒素。有效的疫苗 预防结核病将为个人提供长期的保护 而不需要依靠化疗。保护较大的分段 处于感染风险的人群将减少感染的发生率 结核病并有助于减少疾病的传播，即使是对 免疫受损的人，疫苗对他们可能无效。这个 长期目标是构建一种保护人类的疫苗 人口与结核病的斗争。我们建议鉴定表面蛋白 引起保护性免疫反应的结核分枝杆菌抗原 对抗结核杆菌。指定这类抗原的基因将 被克隆到无毒沙门氏菌疫苗株中，将用于 对小鼠进行免疫，以评估由 克隆的抗原。 第二阶段研究的目标将是评估最好的 重组无毒沙门氏菌疫苗表达的候选抗原 具有保护小鼠和人类免受感染能力的菌株 结核分枝杆菌。 建议的商业应用：重组无毒沙门氏菌 结核分枝杆菌疫苗将在全球范围内用于预防 肺结核。因为几乎所有人的旅行频率都增加了 世界人口的数量，以及由于M。 结核病，结核病的发病率将继续增加，并且 化疗一直无法控制这种疾病。因此，一个 有效的结核病疫苗将具有重大的商业价值。

Tuberculosis remains one of the most significant global health problems today, as it has for centuries. Although the development of chemotherapeutic agents for treating tuberculosis resulted in a dramatic decline in the incidence of tuberculosis from the 1950's until the 1980's, especially in developed countries, the disease has not been contained and is increasing throughout the world. Approximately one third of the world's population is infected with Mycobacterium tuberculosis and three million people die of tuberculosis annually. An alternative approach to chemotherapy for control of infectious diseases has been the development of vaccines against specific components of pathogens or toxins produced by the pathogens. An effective vaccine against tuberculosis would afford long-lasting protection to individuals without having to rely on chemotherapy. Protection of large segments of populations at risk of infection would decrease the incidence of tuberculosis and contribute to reducing spread of disease, even to those who are immunocompromised and for whom a vaccine may be ineffective. The long-term goal is to construct a vaccine that would protect human populations against tuberculosis. We propose to identify surface protein antigens of M. tuberculosis that elicit protective immune responses against the tubercle bacilli. The genes specifying such antigens will be cloned into avirulent Salmonella-vaccine strains, which will be used to immunize mice to evaluate the types of responses elicited by the cloned antigens. The objective during the Phase II study will be to evaluate the best candidate antigens expressed by recombinant avirulent Salmonella vaccine strains for their abilities to protect mice and humans against infection by M. tuberculosis. PROPOSED COMMERCIAL APPLICATION: Recombinant avirulent Salmonella vaccines against M. tuberculosis would be useful worldwide in preventing tuberculosis. Because of increased frequency of travel among nearly all populations of the world and because of the infectious nature of M. tuberculosis, the incidence of TB will continue to increase and chemotherapy has been unable to contain the disease. Therefore, an effective vaccine against TB would have significant commercial value.