The fundamental study for translingual vaccine development

跨语言疫苗开发的基础研究

• 批准号: 21790475
• 负责人: YOSHINO Naoto
• 金额: $ 2.41万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790475/
• 关键词: 粘膜免疫; ワクチン; アジュバント; 免疫学; 舌

Most generic immunization procedures use needles to administer vaccines, which poses the risk of cross-contamination arising from needle reuse. Immunization without physical penetration by needles would greatly increase vaccination ease. In nasal and oral antigen administration, mucosal adjuvants such as cholera toxin (CT) are commonly used to enhance subsequent immune responses. We present herein another novel route of vaccine delivery : translingual immunization (immunization via the surface of the tongue).We found that when ovalbumin (OVA) and CT applied to the tongue surface of C57BL/6 mice stimulated antigen-specific mucosal and systemic immune responses. Increased levels of OVA-specific IgA and IgG antibodies in mucosal secretions and plasma samples were observed, and the enhanced immunity persisted for a full year of observation. Translingual immunization also could induce OVA-specific IgA and IgG Ab-forming cells in the mucosal tissues and spleen. Moreover, in mice translingually immunized with CT, diarrhea induced by oral CT challenge was significantly suppressed. We demonstrated that there was no great difference in translingual, sublingual, intranasal, and intragastric immunization for prevention of CT-induced diarrhea.Translingual immunization with CT as a mucosal adjuvant did not cause weight loss, hypothermia, fervescence, or severe inflammatory response, nor did it affect taste perception. However, these adverse effects were observed in mice in which CT was intramuscularly injected into the tongue. Although use of CT might not necessarily be safe in translingual vaccination, by using much safer mucosal adjuvant, translingual immunization is achieved by simple application of a solution to the surface of the tongue, and it has been important in the development of the novel mucosal route as a useful and easily accessible, noninvasive way to induce vaccine immunity.

大多数通用免疫程序都使用针对疫苗进行疫苗，这构成了针对针头重复使用的交叉污染的风险。没有针头的物理渗透而无需穿针的免疫将大大提高疫苗接种。在鼻和口服抗原给药中，粘膜佐剂（例如霍乱毒素（CT））通常用于增强随后的免疫反应。我们在此提出了另一条新型疫苗输送途径：跨性别免疫（通过舌表面进行免疫接种）。我们发现，当卵形蛋白（OVA）和CT应用于C57BL/6小鼠的舌表面时，刺激了抗原特异性粘膜和全身免疫反应。观察到粘膜分泌和血浆样品中OVA特异性IgA和IgG抗体的水平升高，并且增强的免疫力持续了整整一年的观察。跨性别免疫还可以诱导粘膜组织和脾脏中的OVA特异性IgA和IgG AB形成细胞。此外，在用CT透射免疫的小鼠中，口服CT挑战引起的腹泻受到了显着抑制。我们证明，在预防CT诱导的腹泻的跨语言，舌下，鼻内和胃内免疫无差异上没有差异。然而，在CT肌肉内注射到舌头的小鼠中观察到了这些不良反应。尽管CT的使用可能不一定在跨语言疫苗接种中是安全的，但是通过使用更安全的粘膜佐剂，可以通过简单地将解决方案应用于舌头表面来实现跨性别免疫，并且对于一种有用且易于访问的无创方法来诱导疫苗免疫。

项目成果

Translingual vaccination induces an effective mucosal immunity.

经舌疫苗接种可诱导有效的粘膜免疫。

• 发表时间: 2010
• 作者: Yoshino N;Ami Y;Hirai A;Suzaki Y;Sato S.
• 通讯作者: Sato S.

Intradermal delivery of recombinant vaccinia virus vector DIs induces gut-mucosal immunity.

重组牛痘病毒载体 DI 的皮内递送可诱导肠道粘膜免疫。

• 发表时间: 2010
• 期刊: Scand J Immunol. 72(2)
• 作者: Yoshino N;Kanekiyo M;Hagiwara Y;Okamura T;Someya K;Matsuo K;Ami Y;Sato S;Yamamoto N;Honda M.
• 通讯作者: Honda M.

経舌免疫でのコレラ毒素による下痢抑制効果

经舌免疫抑制霍乱毒素引起的腹泻效果

• 发表时间: 2009
• 作者: 吉野直人;遠藤正宏;菅野祐幸;佐藤成大;Yosei Shimanoe;Yoshiyuki Miyazaki.;吉野直人
• 通讯作者: 吉野直人

新次世代型ワクチンの開発～経舌免疫の効果と安全性～

新型下一代疫苗的开发～经舌免疫的有效性和安全性～

• 发表时间: 2010
• 作者: Tong H;Miyazaki Y;Yamazaki M;Hara H;Waldmann H;Hori S;Yoshida H.;吉野直人
• 通讯作者: 吉野直人

Postinfection passive transfer of KD-247 protects against SHIV-induced CD4^+ T-cell loss in macaque lymphoid tissue.

KD-247 的感染后被动转移可防止猕猴淋巴组织中 SHIV 诱导的 CD4+ T 细胞损失。

• 发表时间: 2009
• 期刊: AIDS 23(12)
• 作者: Murakami T;Eda Y;Nakasone T;Ami Y;Someya K;Yoshino N;Kaizu M;Izumi Y;Matsui H;Shinohara K;Yamamoto N;Honda M.
• 通讯作者: Honda M.