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用佐剂单磷酰脂质 A 免疫接种苍白密螺旋体血红蛋白受体 HgbA 可保护猪免受同源但非异源挑战。

Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge.

机构信息

Division of Infectious Diseases, Department of Medicine, University of North Carolina, 111 Mason Farm Road, CB no. 7031, Chapel Hill, NC 27599, USA.

出版信息

Infect Immun. 2010 Sep;78(9):3763-72. doi: 10.1128/IAI.00217-10. Epub 2010 Jun 28.

Abstract

Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbAI) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbAI dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbAI and 35000HPhgbAII, respectively). Pigs immunized with the nHgbAI/MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbAI but not heterologous strain 35000HPhgbAII, as evidenced by the isolation of only strain 35000HPhgbAII from nHgbAI-immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbAI-immunized animals challenged with strains 35000HPhgbAI but not those challenged with strain 35000HPhgbAII. Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbAI/MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbAI/Freund's vaccine; however, anti-nHgbAI from both studies bound whole cells of 35000HPhgbAI better than 35000HPhgbAII and partially blocked hemoglobin binding to nHgbAI. In conclusion, despite eliciting lower antibody ELISA activity than the nHgbAI/Freund's, the nHgbAI/MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.

摘要

杜克嗜血杆菌是软性下疳的病原体,对血红素有着严格的需求,而血红素只能从其唯一的天然宿主——人类身上获得。此前,我们已经证明,一种包含从杜克嗜血杆菌 I 类菌株 35000HP 中纯化的天然血红蛋白受体 HgbA(nHgbAI)的疫苗制剂,并与弗氏佐剂联合使用,可以为同源性挑战提供完全保护。在当前的研究中,我们研究了 nHgbAI 是否可以替代单磷酰脂质 A(MPL),MPL 是一种已批准用于人类的佐剂,是否可以提供对表达 I 类或 II 类 HgbA 的 35000HP 菌株(分别为 35000HPhgbAI 和 35000HPhgbAII)的挑战的保护。用 nHgbAI/MPL 疫苗免疫的猪只可免受同源 35000HPhgbAI 杜克嗜血杆菌菌株的挑战,但不能免受异源 35000HPhgbAII 菌株的挑战,因为只有 35000HPhgbAII 菌株从 nHgbAI 免疫猪中分离出来。此外,对病变的组织学分析表明,在与 35000HPhgbAI 菌株挑战的模拟免疫和 nHgbAI 免疫动物之间存在明显差异,但与 35000HPhgbAII 菌株挑战的动物之间没有差异。模拟免疫的猪不受任何一种菌株的挑战保护。nHgbAI/MPL 抗血清的酶联免疫吸附试验(ELISA)活性低于用 nHgbAI/Freund 疫苗免疫动物的抗血清活性;然而,来自这两项研究的抗 nHgbAI 均能更好地结合 35000HPhgbAI 的全细胞,而不是 35000HPhgbAII,并且部分阻断了血红蛋白与 nHgbAI 的结合。总之,尽管 nHgbAI/MPL 疫苗引发的抗体 ELISA 活性低于 nHgbAI/Freund,但它可提供对同源性但非异源性 H. 杜克嗜血杆菌的挑战保护,这表明需要使用二价 HgbA 疫苗。

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