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首页> 外文期刊>Infection and immunity >Protective activities in mice of monoclonal antibodies against pertussis toxin.
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Protective activities in mice of monoclonal antibodies against pertussis toxin.

机译：抗百日咳毒素单克隆抗体在小鼠中的保护活性。

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Pertussis toxin (PT) protein, which is the most important protective antigen of Bordetella pertussis, has a hexameric structure composed of five subunits, designated S1 through S5. Immunoprotective activity of 20 different mouse monoclonal antibodies (MAbs) against pertussis toxin, 10 anti-S1, 1 anti-S2, 2 anti-S3, 4 anti-S23, and 3 anti-S4 antibodies, were investigated by aerosol and intracerebral challenges with virulent B. pertussis organisms in mice. Four anti-S1, named 1B7, 1D7, 3F11, and 10D6, and three anti-S23 antibodies, named 11E6, 10B5, and 10C9, showed the highest, and almost complete, protectivity against the aerosol challenge. Mouse protectivity against the intracerebral challenge was significant for these four anti-S1 MAbs but not for any of the three anti-S23 MAbs. Four anti-S1 and two anti-S4 MAbs did not protect the mice against either challenge. The other seven MAbs also showed dose-dependent moderate but significant protection against the aerosol challenge. In the aerosol challenge system, bacterial numbers and amounts of PT detected in the lung and the number of peripheral leukocytes were lower in the mice given the protective MAbs. All mice surviving 5 weeks after the infection produced high titers of antibodies against PT, filamentous hemagglutinin (FHA), and agglutinogens from the challenge organisms. A combination of the protective MAbs 1B7 and 11E6 strongly suppressed the disease and mortality of the mice at smaller amounts than with the anti-PT polyclonal antibody. Although combinations of one of the protective MAb and anti-FHA or anti-agglutinogen 2 also showed extremely high mouse protection without development of symptoms of the disease, antibody titers of the survivors against PT, FHA, and agglutinogens were significantly low. The foregoing results suggest that some important protective epitopes should be in S1 and S2 and/or S3, although there are both differences and similarities in the protective roles between anti-S1 and anti-S23 antibodies and also in the pathogenic mechanisms between aerosol and intracerebral infections. Furthermore, it was suggested that although not only FHA and agglutinogen 2 but also PT have roles as attachment factors, the processes of infection and protection are different between mice immunized with antibody against FHA or agglutinogen 2 and that against PT because the latter mice are also able to neutralize toxicity of PT diffused into the mice.
机译：百日咳毒素（PT）蛋白是百日咳博德特氏菌最重要的保护性抗原，具有由五个亚基组成的六聚体结构，命名为S1至S5。通过气雾剂和脑内挑战研究了20种不同的小鼠单克隆抗体（MAb）对百日咳毒素，10种抗S1、1种抗S2、2种抗S3、4种抗S23和3种抗S4抗体的免疫保护活性。小鼠中的毒性百日咳博德特氏菌。四种名为1B7、1D7、3F11和10D6的抗S1抗体，以及名为11E6、10B5和10C9的三种抗S23抗体，显示出最高的，几乎完全的针对气溶胶攻击的保护性。小鼠对脑内攻击的保护性对于这四种抗S1 MAb而言很重要，但对于这三种抗S23 MAb却没有。四个抗S1和两个抗S4 MAb不能保护小鼠免受任何攻击。其他七个单克隆抗体也显示出剂量依赖性的中度但显着的抗气溶胶攻击保护作用。在气雾剂攻击系统中，给予保护性单克隆抗体的小鼠中，肺中检测到的细菌数量和PT量以及外周白细胞数量较低。感染后存活5周的所有小鼠均产生高滴度的抗PT，丝状血凝素（FHA）和来自攻击生物的凝集素的抗体。与抗PT多克隆抗体相比，保护性MAb 1B7和11E6的组合以较小的量强烈抑制了小鼠的疾病和死亡率。尽管保护性单抗和抗FHA或抗凝集素2之一的组合也显示出极高的小鼠保护作用，而没有疾病症状的发展，但幸存者针对PT，FHA和凝集素的抗体效价却很低。前述结果表明，一些重要的保护表位应该位于S1，S2和/或S3中，尽管抗S1和抗S23抗体之间的保护作用以及气溶胶与脑内的致病机制均存在差异和相似性感染。此外，有人提出，尽管FHA和凝集素原2不仅具有附着因子的作用，但用FHA或凝集素原2抗体免疫的小鼠与PT免疫的小鼠的感染和保护过程是不同的，因为后者也是能够中和扩散到小鼠体内的PT的毒性。

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