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首页> 外文期刊>Infection and immunity >The LTR72 Mutant of Heat-Labile Enterotoxin of Escherichia coli Enhances the Ability of Peptide Antigens To Elicit CD4+ T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin
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The LTR72 Mutant of Heat-Labile Enterotoxin of Escherichia coli Enhances the Ability of Peptide Antigens To Elicit CD4+ T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin

机译：大肠杆菌热不稳定肠毒素的LTR72突变体增强了裸鼠皮肤共施用后肽抗原诱导CD4 + T细胞和分泌Gamma干扰素的能力。

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Application of antigens with an adjuvant onto bare skin is a needle-free and pain-free immunization procedure that delivers antigens to the immunocompetent cells of the epidermis. We tested here the immunogenicity and adjuvanticity of two mutants of heat-labile enterotoxin (LT) of Escherichia coli, LTK63 and LTR72. Both mutants were shown to be immunogenic, inducing serum and mucosal antibody responses. The application of LTK63 and LTR72 to bare skin induced significant protection against intraperitoneal challenge with a lethal dose of LT. In addition, both LT mutants enhanced the capacity of peptides TT:830-843 and HA:307-319 (representing T-helper epitopes from tetanus toxin and influenza virus hemagglutinin, respectively) to elicit antigen-specific CD4+ T cells after coapplication onto bare skin. However, only mutant LTR72 was capable of stimulating the secretion of high levels of gamma interferon. These findings demonstrate that successful skin immunization protocols require the selection of the right adjuvant in order to induce the appropriate type of antigen-specific immune responses in a selective and reliable way. Moreover, the use of adjuvants such the LTK63 and LTR72 mutants, with no or low residual toxicity, holds a lot of promise for the future application of vaccines to the bare skin of humans.
机译：将抗原与佐剂一起应用到裸露皮肤上是一种无针无痛的免疫程序，可将抗原传递至表皮的免疫功能细胞。我们在这里测试了大肠杆菌的两个不耐热肠毒素（LT）突变体LTK63和LTR72的免疫原性和佐剂性。两种突变体均具有免疫原性，可诱导血清和粘膜抗体应答。 LTK63和LTR72在裸露皮肤上的应用诱导了致命剂量的LT对腹膜内攻击的显着保护。此外，两个LT突变体均增强了TT：830-843和HA：307-319肽（分别代表来自破伤风毒素和流感病毒血凝素的T辅助表位）引起抗原特异性CD4 + 在裸露皮肤上共同施用后的T细胞。但是，只有突变体LTR72能够刺激高水平的γ干扰素的分泌。这些发现表明，成功的皮肤免疫方案需要选择正确的佐剂，以便以选择性和可靠的方式诱导适当类型的抗原特异性免疫反应。此外，使用佐剂如LTK63和LTR72突变体而无或具有低残留毒性，对于将来将疫苗应用于人类裸露皮肤具有很大的希望。

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