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兴 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战略 包括使用结核分枝杆菌分泌蛋白，这些蛋白是 存在于培养滤液(CF)中。我们已经为恒河猴接种了疫苗 结核分枝杆菌H37Rv不含LAM的CF.每组两只动物 在没有佐剂的情况下收到的CF，在RIBI佐剂中重新悬浮的CF或 明矾沉淀型碳纤维所有的动物每个月都要喂两次 肌肉注射免疫原，然后进行一次 卡介苗或卡介苗和霍乱毒素B的鼻腔免疫 亚单位。所有单剂免疫原均为1 mg CF。 这些研究的初步结果表明，在 上述免疫方案，对恒河猴的CFs免疫原性 猕猴是有限的。所有患者的结核菌素皮肤试验均为阴性 动物在整个免疫过程中和之后的一系列免疫。不是 体外细胞对CF的显著增殖反应可能是 检测到。抗体反应出现在非常低的水平。 无佐剂免疫的动物。然而，接种了疫苗的动物 明矾-CF或RIBI-CF持续产生中等抗体应答 针对多种特定的抗原，表现出广泛的 分子量。鼻腔免疫接种增加 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 应对配方进行检测以鉴定免疫显性 结核分枝杆菌在恒河猴体内分泌抗原。因此，我们 已经为另外四只猕猴接种了疫苗，以评估是否 免疫原中LAM的存在可能会导致特异性增加 免疫反应。