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Conserved regions of outer membrane proteins as vaccine antigens.

机译：外膜蛋白的保守区域作为疫苗抗原。

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摘要

Nontypeable Haemophilus influenzae (NTHI) is a small, gram-negative bacillus, which causes otitis media in children and lower respiratory infections in adults with chronic obstructive pulmonary disease (COPD). In both otitis media and COPD, patients routinely suffer recurrent episodes of disease. Factors such as health care costs, pain and suffering, and lost work time underscore the need for a vaccine against NTHI.; The ability of NTHI to cause recurrent infections is partly attributable to antigenic variability in several surface-exposed loops of major outer membrane protein P2, which constitutes approximately one-half of the total outer membrane protein of the organism. Loop 5 is highly heterogeneous among strains and contains almost all of the epitopes to which an immune response is mounted when animals are immunized with the whole organism. Adults with COPD make new antibodies to strain-specific epitopes on P2 following infection by NTHI. Thus, immunity against NTHI is most often strain specific, leaving the patient vulnerable to reinfection by other strains.; One approach to vaccine development for NTHI has been to study antigenically conserved outer membrane proteins as potential vaccine antigens. Considering the abundant expression of P2 on the bacterial surface, identification of a conserved, surface exposed region on the P2 molecule would be a significant step towards developing a vaccine against NTHI. Loop 6 of the P2 molecule has the potential to be such a vaccine antigen.; In this study we evaluated the efficacy of the loop 6 region of P2 as a vaccine antigen. The degree of sequence conservation among NTHI was characterized by sequencing the loop 6 region of 108 strains from geographically and clinically diverse sources. Approximately 75% were conserved. Antibodies generated against conserved loop 6 sequences were reactive against multiple strains in western blots and flow cytometry assays. The ability of antibodies raised to conserved loop 6 sequences to kill multiple strains of NTHI was evaluated in bactericidal assays. These data support the concept of using conserved regions of outer membrane proteins as vaccine antigens.; Development of a vaccine against NTHI could be beneficial in several ways. By the age of three years, approximately 80% of all children will have suffered at least one episode of otitis media, 15--40% of which are caused by NTHI. COPD manifests itself in periodic exacerbations caused by lower respiratory tract infections. An estimated 60% of exacerbations are caused by Haemophilus species. Preventing infections due to NTHI could have a significant impact on the morbidity, mortality, and health care costs incurred by COPD in adults and otitis media in children.
机译：非分型流感嗜血杆菌（NTHI）是一种小型革兰氏阴性杆菌，可引起儿童中耳炎和成人慢性阻塞性肺疾病（COPD）的下呼吸道感染。在中耳炎和COPD中，患者通常会反复发作疾病。诸如保健费用，痛苦和苦难以及工作时间损失等因素凸显了对NTHI疫苗的需求。 NTHI引起反复感染的能力部分归因于主要外膜蛋白P2的几个表面暴露环中的抗原变异性，这大约占生物体总外膜蛋白的一半。环5在菌株之间高度异质，并且包含几乎全部的表位，当用整个生物体对动物进行免疫时，该表位会产生免疫反应。患有NT感染的COPD成人在P2上产生针对菌株特异性表位的新抗体。因此，针对NTHI的免疫力通常是菌株特异性的，使患者容易受到其他菌株的再感染。用于NTHI的疫苗开发的一种方法是研究抗原保守的外膜蛋白作为潜在的疫苗抗原。考虑到P2在细菌表面上大量表达，鉴定P2分子上保守的表面暴露区域将是开发针对NTHI的疫苗的重要步骤。 P2分子的环6具有成为这种疫苗抗原的潜力。在这项研究中，我们评估了P2的环6区作为疫苗抗原的功效。 NTHI之间的序列保守程度通过对来自地理和临床上不同来源的108个菌株的环6区域进行测序来表征。约75％是保守的。在western印迹和流式细胞仪测定中，针对保守环6序列产生的抗体对多种菌株具有反应性。在杀菌测定中评估了针对保守的环6序列产生的抗体杀死多种NTHI菌株的能力。这些数据支持使用外膜蛋白的保守区域作为疫苗抗原的概念。抗NTHI疫苗的开发可能会从多种方面受益。到三岁时，大约80％的儿童至少会发作一次中耳炎，其中15--40％是由NTHI引起的。 COPD表现为下呼吸道感染引起的周期性加重。估计有60％的恶化是由嗜血杆菌引起的。预防由NTHI引起的感染可能会对COPD在成人中引起的发病率，死亡率和儿童的中耳炎产生重大影响。

著录项

  • 作者

    Neary, John M.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 113 p.
  • 总页数 113
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

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