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Assessing the immunogenicity of the major outer membrane protein Porin B of Neisseria gonorrhoeae as a vaccine candidate.

机译：评估淋病奈瑟氏球菌主要外膜蛋白Porin B作为候选疫苗的免疫原性。

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摘要

Neisseria gonorrhoeae is a strict human pathogen and the causative agent of the sexually transmitted disease, gonorrhea. Gonococcal (GC) diseases remain one of the most reported sexually transmitted infections (STI) worldwide, representing a significant threat to reproductive health and burden on global health systems, accounting for 541,987 disability adjusted-life years in the year 2011. Infection by N. gonorrhoeae also increases the likelihood of patient acquisition and transmission of human immunodeficiency virus (HIV). Unfortunately, antibiotic treatment to gonococcal diseases is being threatened by the rapid spread of resistance to third-generation cephalosporins, the remaining treatment option used in clinics. The urgency of the situation is compounded by the relative lack of immunological protection conferred by previous infection by the bacterium. In response to the emergence of multidrug resistance, renewed energies are being directed towards the development of an effective, broadly protective vaccine. Difficulties in vaccine development arise from a lack of known correlates of protective immunity; there is no known broadly cross-protective immunity to GC and a truly reflective animal model has not been available. Nonetheless, previous studies have indicated that porins, neisserial major outer membrane proteins, are promising vaccine candidates. PorB makes up over 60% of the bacterium's outer membrane content and is involved in solute and ion exchange, invasion of target host cells, and evasion of host immunity. Porins from both the gonococcus and the meningococcus have been shown to have immunostimulatory activity, boosting B and dendritic (DC) cell proliferation and maturation in the absence of an exogenous adjuvant as mediated by TLR2 and MyD88. Importantly, as a potential vaccine candidate, PorB has relatively low antigenic variability, and can induce bactericidal antibodies. Gonococcal PorB was purified from a genetically modified strain, MS11delP3, which lacks another outer membrane protein, RMP, which is known to induce bactericidal blocking antibodies. PorB was formed into pure protein micelles, termed proteosomes, to protect the integrity of the native trimeric structure. Our study demonstrated that gonococcal PorB is able to stimulate both human embryonic kidney (HEK) cell line that overexpresses TLR2 and mouse primary macrophages (similar to the meningococcal PorB). To test PorB's immunogenicity, mice were immunized three times at two week intervals with PorB and porin specific IgG levels were measured. Unfortunately, PorB elicited lower levels of porin specific IgG than what was expected, which may be due to technical issues. We are currently investigating various possibilities. In addition, further immunization studies shall be carried out to better contextualize these results.
机译：淋病奈瑟菌是一种严格的人类病原体，是性传播疾病淋病的病原体。淋球菌（GC）疾病仍然是全球报告最多的性传播感染（STI）之一，对生殖健康和全球卫生系统构成了重大威胁，2011年占541,987残疾调整生命年。淋病也增加了患者获得和传播人类免疫缺陷病毒（HIV）的可能性。不幸的是，对淋球菌疾病的抗生素治疗正受到对第三代头孢菌素耐药性的迅速扩散的威胁，而第三代头孢菌素是临床上仍在使用的治疗选择。这种情况的紧迫性由于细菌先前的感染而导致相对缺乏免疫保护而变得更加复杂。为了应对多药耐药性的出现，新的能量正致力于开发有效的，具有广泛保护作用的疫苗。疫苗开发的困难是由于缺乏保护性免疫的已知相关性所致。目前尚无针对GC的广泛交叉保护免疫性，还没有真正的反射动物模型。但是，以前的研究表明，猪奈氏球菌（neisserial）主要的外膜蛋白是有希望的疫苗候选者。 PorB占细菌外膜含量的60％以上，涉及溶质和离子交换，靶宿主细胞的入侵以及宿主免疫的逃逸。已显示，在没有外源佐剂（如TLR2和MyD88介导）的情况下，来自淋球菌和脑膜炎球菌的孔蛋白都具有免疫刺激活性，可促进B细胞和树突状细胞（DC）的增殖和成熟。重要的是，作为潜在的疫苗候选物，PorB具有相对较低的抗原变异性，并且可以诱导杀菌抗体。淋球菌PorB是从转基因菌株MS11delP3中纯化的，该菌株缺少另一种外膜蛋白RMP，该蛋白已知可诱导杀菌性阻断抗体。 PorB形成纯蛋白胶束，称为蛋白体，以保护天然三聚体结构的完整性。我们的研究表明，淋球菌PorB能够刺激过度表达TLR2的人类胚胎肾脏（HEK）细胞系和小鼠原代巨噬细胞（类似于脑膜炎球菌PorB）。为了测试PorB的免疫原性，用PorB每两周间隔对小鼠免疫3次，并测量孔蛋白特异性IgG水平。不幸的是，PorB引起的孔蛋白特异性IgG水平低于预期水平，这可能是由于技术问题。我们目前正在研究各种可能性。此外，应进行进一步的免疫研究，以更好地了解这些结果。

著录项

  • 作者

    Le, TuQuynh.;

  • 作者单位

    Boston University.;

  • 授予单位 Boston University.;
  • 学科 Health Sciences Immunology.;Health Sciences General.;Biology Microbiology.
  • 学位 M.S.
  • 年度 2014
  • 页码 62 p.
  • 总页数 62
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:53:18

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