Institute of Biomedicine, Department of Microbiology and Immunology and MIVAC Göteborg University, Göteborg, Sweden.
Vaccine. 2010 Aug 16;28(36):5768-73. doi: 10.1016/j.vaccine.2010.06.032. Epub 2010 Jul 4.
Haemophilus ducreyi causes genital ulceration (chancroid), a sexually transmitted infection and still an important factor which contributes to the spread of HIV in developing countries. The bacterium produces a cytolethal distending toxin (HdCDT) causing cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers. The aim of the study was to induce toxin-neutralizing antibodies in the genital tract of mice. Repeated subcutaneous (sc) immunisations with 5-10microg active HdCDT induced low levels of serum anti-HdCDT IgG without neutralizing capacity. High levels of specific IgG1 antibodies in serum and genital tract were generated after sc immunisations with 10microg formaldehyde detoxified HdCDT toxoid alone and the addition of aluminium salts or RIBI (based on the lipid A moiety) as adjuvant further increased the level of serum antibodies. A high correlation was found between elevated levels of anti-HdCDT IgG in sera, the level of neutralizing activity and the antibody level in genital tract (r=0.8). Thus, induction of high antibody levels specific to HdCDT in the genital tissue can be achieved by parenteral immunisation with the toxoid. The HdCDT toxoid can be considered as a candidate component in vaccine against chancroid.
杜克嗜血杆菌可引起生殖器溃疡（软下疳），这是一种性传播感染，仍然是发展中国家 HIV 传播的重要因素。该细菌产生细胞毒性扩张毒素（HdCDT），导致人类细胞的细胞周期停滞和凋亡/坏死，并加剧溃疡。本研究旨在诱导小鼠生殖道中的毒素中和抗体。用 5-10μg 活性 HdCDT 进行重复皮下（sc）免疫接种可诱导低水平的血清抗 HdCDT IgG，但无中和能力。用 10μg 甲醛解毒 HdCDT 类毒素单独 sc 免疫接种，并添加铝盐或 RIBI（基于脂质 A 部分）作为佐剂，可在血清和生殖道中产生高水平的特异性 IgG1 抗体。血清中抗 HdCDT IgG 水平升高与中和活性和生殖道中抗体水平之间存在高度相关性（r=0.8）。因此，通过用类毒素进行肠外免疫接种可在生殖道组织中诱导针对 HdCDT 的高抗体水平。HdCDT 类毒素可被视为软下疳疫苗的候选成分。
