Williams Ann, Reljic Rajko, Naylor Irene, Clark Simon O, Falero-Diaz Gustavo, Singh Mahavir, Challacombe Stephen, Marsh Philip D, Ivanyi Juraj
Health Protection Agency, Porton Down, Centre for Applied Microbiology and Research (CAMR), Salisbury, UK.
Immunology. 2004 Mar;111(3):328-33. doi: 10.1111/j.1365-2567.2004.01809.x.
We report on a new approach toward protection against tuberculosis, based on passive inoculation with immunoglobulin A (IgA) antibodies. In a mouse model of tuberculous lung infection, intranasal inoculations of mice with an IgA monoclonal antibody (mAb) against the alpha-crystallin antigen of Mycobacterium tuberculosis reduced up to 10-fold the lung bacterial counts at nine days after either aerosol- or intranasal challenge. This effect involved synergism between mAb inoculations shortly before and 3 days after infection. Monomeric IgA reduced the colony-forming unit counts to the same extent as the polymeric IgA, suggesting antibody targeting to Fcalpha, rather than poly-immunoglobulin receptors on infected lung macrophages. The protective effect was of short duration, presumably due to the rapid degradation of the intranasally applied IgA. Our results provide evidence of an alternative approach which could be further developed toward immunoprophylaxis against tuberculosis in immunocompromised subjects.
我们报告了一种基于用免疫球蛋白A(IgA)抗体进行被动接种来预防结核病的新方法。在结核性肺部感染的小鼠模型中,用针对结核分枝杆菌α-晶状体蛋白抗原的IgA单克隆抗体(mAb)经鼻接种小鼠,在气溶胶或经鼻攻击后九天,肺部细菌计数最多可降低10倍。这种效应涉及感染前不久和感染后3天接种mAb之间的协同作用。单体IgA与聚合IgA降低集落形成单位计数的程度相同,这表明抗体靶向Fcalpha,而不是感染的肺巨噬细胞上的多聚免疫球蛋白受体。保护作用持续时间短,可能是由于经鼻应用的IgA迅速降解。我们的结果提供了一种替代方法的证据,该方法可进一步发展用于免疫功能低下受试者的结核病免疫预防。