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Application of mucosal vaccine against upper respiratory tract infections

粘膜疫苗在上呼吸道感染中的应用

基本信息

批准号：
11557126
负责人：
KURONO Yuichi
金额：
$ 8.58万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

1. Production of mucosal vaccines against Haemophilus influenzae (Hi).Outer membrane protein P6 is known to be a most common antigen of Hi. P6 was purified from Hi cultured from a patient with acute otitis media as a mucosal vaccine and recombinant P6 (rP6) was also produced based on the biochemical analysis of P6. Further, recombinant mutant cholera toxin (mCT) fused to rP6 (mCT-rP6) was produced in order to examine the adjuvancity of mCT.2. Mucosal immune responses against recombinant vaccines.Those recombinant vaccines were administered to mice intra-nasally and the mucosal immune responses were compared. In results, IgA responses were not observed in mice immunized with rP6 alone. Although mCT-rP6 induced IgA antibodies in nasal washes of mice, the responses were less than that in mice administered rP6 together with CT. Since CT cannot be used in human because of the toxicity, the results indicate the necessity of developing a new drug-delivery system.3. Immune responses against ovalbumin combined with nanosphere.Nanosphere has been already applied to mucosal vaccine against HIV infection. Nanospheres were combined with ovalbumin in our laboratory and were administered to mice intra-nasally. After three times immunization, the immune responses were investigated. The results showed that nanosphere induced mucosal immune responses ; however, the adjuvancity was less that CT. Those findings indicate that much more concentrated vaccines were needed in order to induce an effective mucosal immunity using nanosphere.4. Immune responses of immune competent cells against endotoxin.Despite the presence of endotoxin in mucosal effusions such as middle ear effusion and paranasal sinus effusion, inflammatory responses were suppressed in those mucosa. In order to clarify the mechanism, tonsillar and nasal mononuclear cells were isolated and stimulated with endotoxin. The results suggest that those immune competent cells might be hi tolerance to endotoxin.

1.抗流感嗜血杆菌（Hi）的粘膜疫苗的生产已知外膜蛋白P6是Hi的最常见抗原。从急性中耳炎患者培养的Hi中纯化P6作为粘膜疫苗，并基于P6的生化分析还产生重组P6（rP 6）。此外，产生融合至rP 6的重组突变霍乱毒素（mCT）（mCT-rP 6）以检查mCT的亲和性。重组疫苗的黏膜免疫反应：将这些重组疫苗鼻内注射给小鼠，并比较黏膜免疫反应。结果，在仅用rP 6免疫的小鼠中未观察到伊加应答。尽管mCT-rP 6在小鼠的鼻洗液中诱导伊加抗体，但应答低于rP 6与CT一起施用的小鼠。由于CT的毒性，不能用于人体，因此，有必要开发一种新的给药系统.卵清蛋白与纳米微球结合的免疫应答研究纳米微球已应用于抗HIV感染的粘膜疫苗。在我们的实验室中将纳米球与卵清蛋白组合，并鼻内给予小鼠。三次免疫后观察免疫应答。结果表明，纳米微球可诱导粘膜免疫应答，但免疫效果不如CT。这些发现表明需要更浓缩的疫苗以使用纳米球诱导有效的粘膜免疫。免疫活性细胞对内毒素的免疫反应尽管在中耳积液和鼻窦积液等粘膜积液中存在内毒素，但这些粘膜中的炎症反应受到抑制。为了阐明其机制，分离扁桃体和鼻单个核细胞并用内毒素刺激。结果提示，这些免疫活性细胞可能对内毒素具有较强的耐受性。