Theus S A, Smulian A G, Steele P, Linke M J, Walzer P D
Department of Internal Medicine, Cincinnati Veterans' Affairs Medical Center, Ohio 45220, USA.
Vaccine. 1998 Jul;16(11-12):1149-57. doi: 10.1016/s0264-410x(98)80113-8.
Pneumocystis carinii, a leading opportunistic pulmonary pathogen, contains a major surface glycoprotein (MSG) which plays a central role in its interaction with the host. Naive Lewis rats were immunized with varying concentrations of purified native MSG and a recombinant form of the protein (MSG-B), placed in a conventional rat colony with exposure to P. carinii, and immunosuppressed with corticosteroids for 10 weeks to induce the development of pneumocystosis. Immunization elicited humoral and cellular immune responses to MSG which persisted throughout the experiment. Compared with animals immunized with ovalbumin or adjuvant alone, the MSG-immunized rats had improved survival (29 vs 66%, p < 0.001), lowered organism burden (log10 9.03 +/- 0.33/lung vs 7.51 +/- 0.38/lung, p < 0.001), less alveolar involvement as assessed by lung histologic score (3.54 +/- 0.42 vs 2.50 +/- 0.42, p < 0.01) and lung weight:body weight ratio (18.2 +/- 1.4 vs 14.6 +/- 1.7, p < 0.01). Animals immunized with MSG-B also showed a significantly lower organism burden, lung histologic score and lung weight:body weight ratio than control rats. Thus, MSG is the first P. carinii antigen which can elicit a protective response in the immunosuppressed rat model of pneumocystosis and this finding supports the rationale of developing a P. carinii vaccine.
卡氏肺孢子菌是一种主要的机会性肺部病原体,它含有一种主要表面糖蛋白(MSG),该蛋白在其与宿主的相互作用中起核心作用。将不同浓度的纯化天然MSG和该蛋白的重组形式(MSG-B)免疫未接触过病原体的Lewis大鼠,将其置于常规大鼠群落中使其接触卡氏肺孢子菌,并用皮质类固醇免疫抑制10周以诱导肺孢子菌病的发展。免疫引发了对MSG的体液免疫和细胞免疫反应,且在整个实验过程中持续存在。与仅用卵清蛋白或佐剂免疫的动物相比,用MSG免疫的大鼠存活率提高(29%对66%,p<0.001),病原体负荷降低(每肺log10 9.03±0.33对7.51±0.38,p<0.001),通过肺组织学评分评估的肺泡受累程度较轻(3.54±0.42对2.50±0.42,p<0.01),肺重量与体重比降低(18.2±1.4对14.6±1.7,p<0.01)。用MSG-B免疫的动物与对照大鼠相比,病原体负荷、肺组织学评分和肺重量与体重比也显著降低。因此,MSG是第一种能在免疫抑制的肺孢子菌病大鼠模型中引发保护性反应的卡氏肺孢子菌抗原,这一发现支持了开发卡氏肺孢子菌疫苗的理论依据。