Mucosal Vaccines : Vectors and Adjuvants for Novel Th1 and Th2 cells

这项国际合作研究项目的一个主要目标是研究包括沙门氏菌毒素(CT)、不稳定肠毒素(LT)和IL-12在内的粘膜调节剂在IgA诱导和效应室诱导抗原特异性Th1和Th2细胞的分子和细胞机制。我们的结果表明，疫苗蛋白抗原和CT作为粘膜佐剂的粘膜免疫可引起显性的Th2型应答，从而在全身和粘膜间隔产生抗原特异性的Ig G和Ig A抗体。与CT不同，联合应用LT作为粘膜调节剂可导致抗原特异性Th1和Th2细胞的产生。此外，研究表明，在活体内，粘膜给药的IL-12将主要的Th2反应转变为Th1型反应。这些发现表明，使用不同的粘膜调节剂，可以模拟黏膜和全身Th1/Th2和B细胞反应的结果。这些有趣而重要的发现将有助于Mucosal疫苗的开发，这些发现是大阪大学和阿拉巴马大学伯明翰分校(UAB)共同努力的结果。通过这个项目，28篇原创论文和15篇综述发表在《美国进出口医学杂志》、《美国国家科学院院刊》、《免疫学》、《胃肠病学》等高质量期刊上。我谨代表大阪大学和UAB粘膜免疫实验室，对我们为建立黏膜免疫学跨太平洋研究体系的新概念所给予的支持表示感谢。

A major goal of this Internationa1 Collaborative Research Project was to investigate molecular and cellular mechanisms of mucosal modulators including choelera toxin (CT), Labile enterotoxin (LT) and IL-12 for the induction of antigen-specific Th1 and Th2 cells in the IgA inductive and effector compartments. Our findings demonstrated that mucosal immunization of vaccine protein antigen and CT as mucosal adjuvant resulted in the dominant Th2 type response which lead to the generation of antigen-specific IgG and IgA antibodies in both systemic and mucopsal compartments. In contrast to CT,co-administered LT as a mucosal modulator resulted in the generation of both antigen-specific Th1 and Th2 cells. Further, it was shown that mucosally-administered IL-12 shifts a dominant Th2 to Th1 type response in vivo. These findings suggested that using the different mucosal modulators, one can mimic outcome of mucosal and systemic Th1/Th2 and B cell responses. These interesting and important findings which will contribute for the development of Mucosal Vaccine were generated by the collaborative effort between Osaka University and the University of Alabama at Birmingham (UAB). Through this project, 28 original articles and 15 reviews were published in high quality journals such as J.Exp.Med., Proc.Natl.Acad.Sci.USA., J.Immunol., Gastroenterology and etc.On behalf of Osaka and UAB Mucosal Immunology Laboratories, I would like to express our appreciation for this kind support to establish new concept for Mucosal immunology Trans-Pacific Research System.