Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Infect Immun. 2011 Aug;79(8):3168-77. doi: 10.1128/IAI.00017-11. Epub 2011 Jun 6.
Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.
杜克雷嗜血杆菌是软下疳的病原体,对血红素有必需的需求。杜克雷嗜血杆菌通过其表面表达的 TonB 依赖性转运体从其人类宿主中获取血红素。在杜克雷嗜血杆菌基因组中编码的 3 种 TonB 依赖性转运体中,只有血红蛋白受体 HgbA 是在软下疳实验性人类模型的早期感染阶段所必需的。用 Freund 佐剂或单磷酰脂质 A 作为佐剂,用天然制备的 HgbA(nHgbA)进行主动免疫,可在软下疳实验性猪模型中完全保护。为了确定转移抗 nHgbA 血清是否足以提供保护,在软下疳实验性猪模型中进行了使用 nHgbA 抗血清的被动免疫实验。接受这种 nHgbA 抗血清的猪可免受同源但非异源的挑战。针对 nHgbA 诱导的被动转移多克隆抗体结合了 H. ducreyi 的表面,并部分阻断了 nHgbA 对血红蛋白的结合,但没有杀菌作用。综上所述,这些数据表明针对 HgbA 疫苗的体液免疫反应可预防 H. ducreyi 感染,可能是通过防止必需营养血红素的获取。