中文摘要：研究构建了一种新型粘膜佐剂，该佐剂将霍乱毒素B亚单元以HIV-1 Tat蛋白转导域（PTD）代替，通过非特异性绑定到细胞表面能有效促进融合蛋白进入胞浆。试验比较了佐剂Tat PTD-CTA1-Tat PTD (TCTA1T)与霍乱毒素（CT）的特性和毒性。结果表明：与CT佐剂相比，皮内传递携带TCTA1T的卵清蛋白能够显著提高卵清特异性系统和粘膜抗体反应；TCTA1T诱导产生的细胞毒性T淋巴细胞活性显著高于突变TCTA1T（TmCTA1T）诱导的细胞毒性T淋巴细胞活性。此外，将流感M2蛋白与TCTA1T联合免疫能够产生对抗致死流感病毒的保护作用。重要的是，与CT相比，TCTA1T不会产生针对自身抗原的血浆IgG抗体反应，因此不会产生毒性作用。这些结果表明， TCTA1T是一种安全、有效的粘膜免疫佐剂。
外文摘要：Potential use of cholera toxin (CT) as a mucosal vaccine adjuvant has been documented in a variety of animal models. However, native CT is highly toxic to be used as a mucosal adjuvant in humans. Here, we demonstrate a new approach to generate a mucosal adjuvant by replacing the B subunit of CT with HIV-1 Tat protein transduction domain (PTD), which efficiently delivers fusion proteins into the cell cytoplasm by unspecific binding to cell surface. We compared the adjuvanticity and toxicity of Tat PTD-CTA1-Tat PTD (TCTA1T) with those of CT. Our results indicate that intranasal (i.n.) delivery of ovalbumin (OVA) with TCTA1T significantly augments the OVA-specific systemic and mucosal antibody responses to levels comparable to those seen with CT adjuvant. Moreover, in vivo cytotoxic T lymphocyte activity elicited by TCTA1T was significantly higher than that elicited by a mutant TCTA1T (TmCTA1T) lacking ADP-ribosyltransferase function. In addition, coadministration of influenza M2 protein with TCTA1T conferred near complete protection against lethal influenza virus challenge. Importantly, TCTA1T, in contrast to CT, did not induce serum IgG antibody responses to itself and was shown to be nontoxic. These results suggest that TCTA1T may be a safe and effective adjuvant when given by mucosal routes.
外文关键词：HEAT-LABILE ENTEROTOXIN; HUMAN-IMMUNODEFICIENCY-VIRUS; ESCHERICHIA-COLI; TAT PROTEIN; IMMUNE-RESPONSES; NONHUMAN-PRIMATES; VACCINE ADJUVANT; DELIVERY; IMMUNIZATION; ANTIGENS
作者：Shim, BS; Cheon, IS; Lee, E; Park, SM; Choi, Y; Jung, DI; Yang, E; Choi, JA; Chun, JY; Kim, JO; Yun, CH; Czerkinsky, C; Song, MK
作者单位：韩国疫苗研究所
期刊名称：JOURNAL OF IMMUNOLOGY RESEARCH
期刊影响因子：4.79
出版年份：2018
出版刊次：3
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