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: 6247327
• 负责人: ROBERTA ATTANASIO
• 金额: $ 7.55万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247327
• 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.

持续的坚持和最近的复苏 结核病强调需要开发一种改进的 疫苗。 开发此类疫苗的潜在策略 包括使用结核分枝杆菌分泌的蛋白质，这些蛋白质是 存在于培养滤液 (CF) 中。 我们对恒河猴进行了免疫 含有结核分枝杆菌 H37Rv 无 LAM CF。 每组两只动物 在没有佐剂的情况下接受 CF，将 CF 重悬于 RIBI 佐剂中或 明矾沉淀CF。 所有动物每月接受两次 肌肉注射免疫原，然后单次注射 CF 或 CF 和霍乱毒素 B 的鼻内免疫 亚基。 所有单剂量的免疫原均包含 1 mg CF。 这些研究的初步结果表明，继 上述免疫方案，恒河猴中的 CF 免疫原性 猕猴数量有限。 全部结核菌素皮试均为阴性 在一系列免疫接种期间和之后的动物。 不 CF 的显着体外细胞增殖反应可能是 检测到。 抗体反应的水平非常低 动物在没有佐剂的情况下进行免疫。 然而，接种了疫苗的动物 alum-CF 或 RIBI-CF 始终产生中等抗体反应 针对表现出广泛范围的多种特异性抗原 分子量。 鼻内免疫诱导增加 在先前免疫过的动物中产生特异性抗体 CF-佐剂。 额外的免疫方案和佐剂 应测试制剂以鉴定免疫优势 结核分枝杆菌在恒河猴中分泌抗原。 因此，我们 对另外四只猕猴进行了免疫接种，以评估是否 免疫原中 LAM 的存在可能会导致特异性抗体的增加 免疫反应。