Low-frequency ultrasound as a transcutaneous immunization adjuvant

Low-frequency ultrasound as a transcutaneous immunization adjuvant
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DOI:
10.1016/j.vaccine.2005.02.027
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发表时间:
2005-05-31
期刊:
影响因子:
5.5
通讯作者:
Mitragotri, S
Mitragotri, S
中科院分区:
医学3区
文献类型:
--
作者:
Tezel, A;Paliwal, S;Mitragotri, S

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由于皮肤免疫细胞(尤其是朗格汉斯细胞)向免疫系统呈递抗原的独特能力,经皮疫苗递送提供了一种有利的免疫模式。朗格汉斯细胞在活化后迁移到局部淋巴结,并导致全身和粘膜免疫应答的产生。然而,疫苗的简单局部应用不能在皮肤中递送足够量的抗原以产生足够的免疫应答。联合施用强佐剂如霍乱毒素或侵入性皮肤擦伤通常是必要的,以通过局部疫苗应用诱导足够的免疫应答。在这里,我们报告使用低频超声作为一种有效的物理佐剂成功的经皮免疫(TCI)。使用破伤风类毒素作为模型疫苗,我们表明,低频超声增强局部应用破伤风类毒素诱导的免疫反应。超声的辅助作用部分是由超声应用后破伤风类毒素向皮肤中的增强递送和部分是由超声TCI后免疫细胞的激活来解释的。这些研究证明了通过TCI产生有效的全身免疫应答,而不使用毒素佐剂或皮肤擦伤。超声TCI提供了一种无针无痛的免疫模式。(c)2005爱思唯尔有限公司保留所有权利。
Percutaneous vaccine delivery offers an advantageous mode of immunization due to the unique ability of cutaneous immune cells, especially Langerhans cells, to present antigens to the immune system. Langerhans cells, upon activation, migrate to the regional lymph nodes and lead to the generation of systemic and mucosal immune responses. However, simple topical application of vaccines does not deliver sufficient amounts of antigen in the skin to generate an adequate immune response. Co-administration of strong adjuvants such as cholera toxin or invasive skin abrasion is usually necessary to induce an adequate immune response by topical vaccine application. Here, we report on the use of low-frequency ultrasound as a potent physical adjuvant for successful transcutaneous immunization (TCI). Using tetanus toxoid as a model vaccine, we show that low-frequency ultrasound enhances the immune response induced by topical application of tetanus toxoid. The adjuvant effect of ultrasound is partly explained by the enhanced delivery of tetanus toxoid into the skin after ultrasound application and partly by the activation of immune cells after ultrasonic TCI. These studies demonstrate generation of a potent systemic immune response through TCI without using toxin adjuvants or skin abrasion. Ultrasonic TCI offers a needle-free and painless mode of immunization. (c) 2005 Elsevier Ltd. All rights reserved.