Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins
Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins
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DOI：
10.1128/iai.72.5.2659-2670.2004
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发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
Brodeur, BR
中科院分区：
文献类型：
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作者：
Hamel, J;Charland, N;Brodeur, BR
由于存在至少90种抗原性不同的衣壳血清型，肺炎链球菌疫苗的开发变得复杂起来。普通的基于蛋白质的疫苗可以代表预防肺炎球菌感染的最佳策略，无论是哪种血清型。在本研究中，肺炎链球菌基因组文库的免疫筛选使一个新的免疫蛋白靶标BVH-3得以鉴定。我们证明，BVH-3免疫小鼠可引起对实验性脓毒症和肺炎的保护性免疫。序列分析表明，BVH-3基因在物种内高度保守。由于BVH-3蛋白在其氨基末端与其他肺炎球菌蛋白显示同源性，因此确定保护作用是由于同源区域还是蛋白质特异性区域是有意义的。使用重组BVH-3和BVH-3相关蛋白片段作为抗原的免疫保护研究允许将表面暴露的和保护性表位定位在蛋白质特异性的羧基末端，从而确立了BVH-3不同于以往报道的其他保护性蛋白抗原。用包含BVH-3羧基末端区域和BVH-3相关蛋白的嵌合蛋白免疫，通过靶向两种表面肺炎球菌成分，提高了保护作用。因此，BVH-3和嵌合蛋白作为控制肺炎球菌疾病的疫苗成分具有很强的前景。
The development of a vaccine against Streptococcus pneumoniae has been complicated by the existence of at least 90 antigenically distinct capsular serotypes. Common protein-based vaccines could represent the best strategy to prevent pneumococcal infections, regardless of serotype. In the present study, the immunoscreening of an S. pneumoniae genomic library allowed the identification of a novel immune protein target, BVH-3. We demonstrate that immunization of mice with BVH-3 elicits protective immunity against experimental sepsis and pneumonia. Sequence analysis revealed that the bvh-3 gene is highly conserved within the species. Since the BVH-3 protein shows homology at its amino-terminal end with other pneumococcal proteins, it was of interest to determine if protection was due to the homologous or to the protein-specific regions. Immunoprotection studies using recombinant BVH-3 and BVH-3-related protein fragments as antigens allowed the localization of surface-exposed and protective epitopes at the protein -specific carboxyl termini, thus establishing that BVH-3 is distinct from other previously reported protective protein antigens. Immunization with a chimeric protein comprising the carboxyl-terminal regions of BVH-3 and of a BVH-3-related protein improved the protection by targeting two surface pneumococcal components. Thus, BVH-3 and the chimeric protein hold strong promise as vaccine components to control pneumococcal disease.