Kayamuro Hiroyuki, Yoshioka Yasuo, Abe Yasuhiro, Kamada Haruhiko, Tsunoda Shin-ichi, Tsutsumi Yasuo
National Institute of Biomedical Innovation, Laboratory of Pharmaceutical Proteomics, Ibaraki, Osaka, Japan.
Yakugaku Zasshi. 2010 Jan;130(1):55-61. doi: 10.1248/yakushi.130.55.
A large number of emerging pathogens, such as severe acute respiratory syndrome (SARS), human immunodeficiency virus (HIV), and influenza virus are mucosally transmitted and must cross mucosal barriers to infect the host. Thus, to induce a maximal protective effect, it is desirable to apply vaccines by the mucosal route where virus infections start. Mucosal vaccines administered either orally or nasally have been shown to be effective in inducing antigen-specific immune responses at both systemic and mucosal compartments. However the mucosal antigen-specific immune response is weak because most protein antigens can evoke only a weak immune response when they are applied mucosally. Therefore, one strategy to overcome the weakness of the immune response is a co-administration of mucosal adjuvant with the vaccine antigen. Unfortunately, the development of safe and effective mucosal adjuvant has proved to be challenging. Cytokines are promising adjuvants because they are human-derived safe material and display potent immune-modulating functions. In this regards, we have created a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and resistance to proteases. In this report, we examined the potential of mTNF-K90R as a mucosal adjuvant and evaluated its effectiveness and safety.
大量新出现的病原体，如严重急性呼吸综合征（SARS）、人类免疫缺陷病毒（HIV）和流感病毒，都是通过黏膜传播的，并且必须穿过黏膜屏障才能感染宿主。因此，为了诱导最大的保护作用，理想的做法是在病毒感染开始的部位通过黏膜途径接种疫苗。口服或鼻内接种的黏膜疫苗已被证明在诱导全身和黏膜部位的抗原特异性免疫反应方面是有效的。然而，黏膜抗原特异性免疫反应较弱，因为大多数蛋白质抗原经黏膜接种时只能引发较弱的免疫反应。因此，克服免疫反应弱点的一种策略是将黏膜佐剂与疫苗抗原共同给药。不幸的是，事实证明开发安全有效的黏膜佐剂具有挑战性。细胞因子是很有前景的佐剂，因为它们是源自人类的安全物质，并具有强大的免疫调节功能。在这方面，我们制备了一种突变型肿瘤坏死因子-α（TNF-α），即mTNF-K90R，它具有高生物活性且对蛋白酶具有抗性。在本报告中，我们研究了mTNF-K90R作为黏膜佐剂的潜力，并评估了其有效性和安全性。
