The fundamental study for translingual vaccine development

大多数通用免疫程序使用针头接种疫苗，这造成针头重复使用造成交叉污染的风险。没有针头物理穿透的免疫接种将大大增加疫苗接种的便利性。在鼻和口服抗原施用中，粘膜佐剂如霍乱毒素（CT）通常用于增强随后的免疫应答。本文介绍了另一种新的疫苗递送途径：舌面免疫（通过舌表面免疫），我们发现当卵清蛋白（OVA）和CT应用于C57 BL/6小鼠的舌表面时，刺激抗原特异性粘膜和全身免疫应答。在粘膜分泌物和血浆样本中观察到OVA特异性伊加和IgG抗体水平增加，并且免疫增强持续了整整一年的观察。经舌免疫还可在粘膜组织和脾脏中诱导OVA特异性伊加和IgGAb形成细胞。此外，在用CT双舌免疫的小鼠中，由口服CT攻击引起的腹泻被显著抑制。我们证明舌下、舌下、鼻内和胃内免疫对预防CT诱导的腹泻没有很大差异，以CT作为粘膜佐剂的舌下免疫不会引起体重减轻、体温降低、发热或严重的炎症反应，也不会影响味觉。然而，在将CT肌内注射到舌头中的小鼠中观察到这些不良反应。尽管CT在舌内接种中的使用可能不一定安全，但通过使用更安全的粘膜佐剂，通过将溶液简单地应用于舌表面来实现舌内免疫，并且在开发新的粘膜途径作为诱导疫苗免疫的有用且容易获得的非侵入性方式中一直很重要。

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.