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用于分析保护性抗体的小鼠肺炎球菌肺炎和菌血症模型

Pneumococcal pneumonia and bacteremia model in mice for the analysis of protective antibodies.

作者信息

Saeland E, Vidarsson G, Jonsdottir I

机构信息

National University Hospital, Department of Immunology, Reykjavik, Iceland.

出版信息

Microb Pathog. 2000 Aug;29(2):81-91. doi: 10.1006/mpat.2000.0363.

DOI:10.1006/mpat.2000.0363
PMID:10906263
Abstract

Pneumococci cause infection by colonizing the nasopharynx and invading the mucosal surfaces. Infection models in mice, where the natural route of infection is mimicked, may be useful to study antibody mediated protection against pneumococcal pneumonia and bacteremia. We have established a pneumococcal pneumonia and bacteremia model in mice and investigated the protective capacity of human antibodies. Intranasal challenge with serotypes 1, 3, 6A and 8 caused lung infection and bacteremia which was lethal. Serotype 6B caused low, but detectable, infection and other serotypes tested were not virulent. Passive immunization with a human IgG preparation i.p. protected mice in a dose dependent manner against bacteremia caused by the virulent serotypes (except serotype 3) and partially or completely cleared pneumococci from the lungs of mice infected with serotypes 1, 6A and 8. Adsorption of antibodies with homologous capsular polysaccharides eliminated protection against disease but adsorption with cell wall polysaccharides (CWPS) did not. Furthermore, a good correlation was observed between protection of sera in vivo and opsonic activity in vitro. The results indicate that the model may be useful to analyse the levels, isotypes, specificity and other characteristics of human antibodies which protect against pneumococcal infection and to evaluate the protective potential of pneumococcal vaccine candidates.

摘要

肺炎球菌通过在鼻咽部定植并侵入黏膜表面引发感染。在小鼠中模拟自然感染途径的感染模型,可能有助于研究抗体介导的针对肺炎球菌肺炎和菌血症的保护作用。我们已在小鼠中建立了肺炎球菌肺炎和菌血症模型,并研究了人源抗体的保护能力。用1、3、6A和8型血清型进行鼻内攻击会导致致命的肺部感染和菌血症。6B型血清型导致的感染程度较低但可检测到,而测试的其他血清型则无致病性。腹腔注射人IgG制剂进行被动免疫以剂量依赖的方式保护小鼠免受由致病血清型(3型血清型除外)引起的菌血症,并部分或完全清除感染1、6A和8型血清型的小鼠肺部的肺炎球菌。用同源荚膜多糖吸附抗体可消除对疾病的保护作用,但用细胞壁多糖(CWPS)吸附则不会。此外,在体内血清的保护作用与体外调理活性之间观察到良好的相关性。结果表明,该模型可能有助于分析针对肺炎球菌感染的人源抗体的水平、亚型、特异性和其他特征,并评估肺炎球菌候选疫苗的保护潜力。

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