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首页> 美国卫生研究院文献>Infection and Immunity >Parenteral Adjuvant Activities of Escherichia coli Heat-Labile Toxin and Its B Subunit for Immunization of Mice against Gastric Helicobacter pylori Infection
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Parenteral Adjuvant Activities of Escherichia coli Heat-Labile Toxin and Its B Subunit for Immunization of Mice against Gastric Helicobacter pylori Infection

机译：大肠杆菌的热不稳定毒素及其B亚基的肠胃外佐剂活性可免疫小鼠抵抗幽门螺杆菌感染。

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The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric challenge with H. pylori. Control mice were immunized orally with urease plus LT, a regimen shown previously to protect against H. pylori gastric infection. Parenteral immunization using either LT or LTB as adjuvant protected mice against H. pylori challenge as effectively as oral immunization and enhanced urease-specific immunoglobulin G (IgG) responses in serum as effectively as aluminum hydroxide adjuvant. LT and LTB had adjuvant activity at subtoxic doses and induced more consistent antibody responses than those observed with oral immunization. A mixture of a low dose of LT and a high dose of LTB stimulated the highest levels of protection and specific IgG in serum. Urease-specific IgG1 and IgG2a antibody subclass responses were stimulated by all immunization regimens tested, but relative levels were dependent on the adjuvant used. Compared to parenteral immunization with urease alone, LT preferentially enhanced IgG1, while LTB or the LT-LTB mixture preferentially enhanced IgG2a. Parenteral immunization using LT or LTB as adjuvant also induced IgA to urease in the saliva of some mice. These results show that LT and LTB stimulate qualitatively different humoral immune responses to urease but are both effective parenteral adjuvants for immunization of mice against H. pylori infection.
机译：大肠杆菌的热不稳定毒素（LT）是一种强效的粘膜佐剂，已被用来诱导小鼠抵抗猫粪便和幽门螺杆菌感染的保护性免疫。我们研究了重组幽门螺杆菌或其B亚基（LTB）是否在小鼠中通过非肠道途径与幽门螺杆菌尿素酶抗原结合后具有佐剂活性。在用幽门螺杆菌进行胃内攻击之前，用脲酶加LT，重组LTB或LT和LTB的组合对小鼠进行皮下或皮内免疫。对照小鼠经尿素酶加LT口服免疫，该方案先前已证明可预防幽门螺杆菌胃部感染。使用LT或LTB作为佐剂的肠胃外免疫可以像口服免疫一样有效地保护小鼠抵抗幽门螺杆菌攻击，并且可以像氢氧化铝佐剂一样有效地增强血清中脲酶特异性免疫球蛋白G（IgG）的应答。与口服免疫相比，LT和LTB在亚毒性剂量下具有佐剂活性，并诱导出更一致的抗体反应。低剂量的LT和高剂量的LTB的混合物刺激了血清中最高水平的保护和特异性IgG。所有测试的免疫方案均刺激了脲酶特异性IgG1和IgG2a抗体亚类应答，但相对水平取决于所用佐剂。与仅使用脲酶的肠胃外免疫相比，LT优先增强IgG1，而LTB或LT-LTB混合物优先增强IgG2a。使用LT或LTB作为佐剂的肠胃外免疫也可诱导某些小鼠唾液中的IgA产生脲酶。这些结果表明，LT和LTB在质上刺激了对脲酶的不同体液免疫应答，但是它们都是用于免疫小鼠抵抗幽门螺杆菌感染的有效的肠胃外佐剂。

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