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

这个国际合作研究项目的主要目标是研究粘膜调节剂的分子和细胞机制，包括霍乱毒素（CT）、不稳定肠毒素（LT）和IL-12，以诱导抗原特异性Th1和Th2细胞进入IgA诱导室和效应室。我们的研究结果表明，疫苗蛋白抗原和CT作为粘膜佐剂的粘膜免疫导致主要的Th2型反应，导致在全身和粘膜隔室中产生抗原特异性IgG和IgA抗体。与CT相比，作为粘膜调节剂的联合给药LT导致抗原特异性Th1和Th2细胞的产生。此外，研究表明，粘膜给药IL-12在体内将主导的Th2型反应转变为Th1型反应。这些发现表明，使用不同的粘膜调节剂，可以模拟粘膜和全身Th1/Th2和B细胞反应的结果。大阪大学和阿拉巴马大学伯明翰分校（UAB）的合作产生了这些有趣而重要的发现，这些发现将有助于粘膜疫苗的开发。通过该项目，在J.Exp.Med等高质量期刊上发表了28篇原创文章和15篇综述。, Proc.Natl.Acad.Sci.USA。, J.Immunol。我谨代表大阪市和UAB粘膜免疫学实验室对这种支持表示感谢，以建立粘膜免疫学跨太平洋研究系统的新概念。

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.