Division of Infectious Diseases, Department of Medicine, University of North Carolina, 111 Mason Farm Road, CB no. 7031, Chapel Hill, NC 27599, USA.
Infect Immun. 2010 Sep;78(9):3763-72. doi: 10.1128/IAI.00217-10. Epub 2010 Jun 28.
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.
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。