IMMUNOGENICITY OF MYCOBACTERIUM TB CULTURE FILTRATE PROTEINS IN RHESUS:VACCINE

恒河猴中结核分枝杆菌培养物滤过蛋白的免疫原性：疫苗

• 批准号: 2711837
• 金额: $ 3.43万
• 依托单位: EMORY UNIVERSITY
• 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/2711837
• 关键词: Mammalia; Primates; animal tissue; bacteria; communicable diseases; immunology; lymphatic system; vaccines

The continuous persistence and the recent resurgence of tuberculosis emphasize the need for the development of an improved vaccine. Potential strategies for the development of such a vaccine include the use of M. tuberculosis secreted proteins, which are present in culture filtrates (CF). We have immunized rhesus macaques with M. tuberculosis H37Rv LAM-free CF. Groups of two animals each received CF in absence of adjuvant, CF resuspended in RIBI adjuvant or alum-precipitated CF. All animals were given two monthly intramuscular injections of the immunogens, followed by a single intranasal immunization of either CF or CF and cholera toxin B subunit. All single doses of immunogens consisted of 1 mg CF. Preliminary results from these studies indicate that, following the above described immunization protocol, the CF immunogenicity in rhesus macaque is limited. The tuberculin skin test was negative in all animals throughout and after the series of immunizations. No significa nt in vitro cellular proliferative responses to CF could be detected. Antibody responses were present at a very low level in animals immunized without adjuvant. However, animals inoculated with alum-CF or RIBI-CF produced moderate antibody responses consistently directed to multiple specific antigens exhibiting a broad range of molecular weights. Intranasal immunizations induced increased production of specific antibodies in animals previously immunized with CF-adjuvant. Additional immunization protocols and adjuvant formulations should be tested for the identification of immunodominant M. tuberculosis secreted antigens in rhesus macaques. Therefore, we have immunized four additional macaques to assess whether or not presence of LAM in the immunogens may induce an increase in specific immune responses.

持续存在和最近的复苏， 结核病强调需要发展一种改进的 疫苗 开发这种疫苗的潜在策略 包括M的使用。结核杆菌分泌的蛋白质， 存在于培养皿中（CF）。 我们已经免疫了恒河猴 与M.结核病H37 Rv无LAM CF. 每组两只动物 在不存在佐剂的情况下接受CF，将CF重悬于RIBI佐剂中，或 铝沉淀CF. 所有动物每月给予两次 肌内注射免疫原，然后单次 CF或CF和霍乱毒素B鼻内免疫 亚单位 所有单剂量的免疫原均由1 mg CF组成。 这些研究的初步结果表明， 上述免疫方案，恒河猴中的CF免疫原性 猕猴是有限的。 结核菌素皮试均为阴性 在整个免疫过程中和免疫后的动物。 没有 在体外细胞增殖反应CF可以显着， 检测到 抗体反应在一个非常低的水平， 无佐剂免疫的动物。 然而，接种了 alum-CF或RIBI-CF一致地产生中等抗体应答 针对表现出广泛的免疫反应性的多种特异性抗原， 分子量 鼻内免疫诱导增加 在先前免疫的动物中产生特异性抗体 CF-佐剂。 其他免疫方案和佐剂 应检测制剂以鉴定免疫显性 M.结核病在恒河猴中分泌抗原。 所以我们 给另外四只猕猴注射了疫苗， LAM在免疫原中的存在可诱导特异性免疫应答的增加。 免疫反应。