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经鼻腔接种 OMP 纳米乳剂疫苗诱导对 17 kDa OMPA 洋葱伯克霍尔德氏菌多肽的免疫应答并保护小鼠免受肺部感染。

Induction of immune response to the 17 kDa OMPA Burkholderia cenocepacia polypeptide and protection against pulmonary infection in mice after nasal vaccination with an OMP nanoemulsion-based vaccine.

机构信息

Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), University of Michigan, 9220 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-5648, USA.

出版信息

Med Microbiol Immunol. 2010 May;199(2):81-92. doi: 10.1007/s00430-009-0137-2. Epub 2009 Dec 6.

Abstract

Burkholderia cepacia complex (Bcc) are opportunistic bacteria associated with life-threatening illness in persons with cystic fibrosis. Once Bcc colonization is established, these antimicrobial-resistant and biofilm-forming bacteria are difficult to eradicate and are associated with increased rates of morbidity and mortality. At present, no vaccines are available to prevent the Bcc infection. There is currently a paucity of published information regarding the development of vaccines designed to prevent Burkholderia colonization. This work expands on the recent studies published by Bertot et al. [Infect Immun 75(6):2740-2752, 2007], where successful protective immune responses were generated in mice using a B. multivorans OMP-based vaccine. Here, we evaluate an experimental mucosal vaccine against Bcc using a novel mucosal adjuvant (nanoemulsion) and a novel B. cenocepacia-based OMP antigen. The OMP antigen derived from B. cenocepacia was mixed with either nanoemulsion or with PBS and delivered intranasally to CD-1 mice. Serum analysis showed robust IgG and mucosal secretory IgA immune responses in vaccinated versus control mice. The antibodies had cross-neutralizing activity against both B. cenocepacia and B. multivorans species. We found that immunized mice were protected against pulmonary colonization with B. cenocepacia. We have also identified that a 17 kDa OmpA-like protein highly conserved between Burkholderia and Ralstonia species as a new immunodominant epitope in mucosal immunization.

摘要

洋葱伯克霍尔德菌复合群(Bcc)是与囊性纤维化患者危及生命的疾病相关的机会性细菌。一旦 Bcc 定植建立,这些具有抗微生物耐药性和生物膜形成能力的细菌就很难被根除,并与发病率和死亡率的增加有关。目前,尚无疫苗可预防 Bcc 感染。目前,关于旨在预防伯克霍尔德菌定植的疫苗开发的已发表信息很少。这项工作扩展了 Bertot 等人最近发表的研究[Infect Immun 75(6):2740-2752, 2007],其中使用 B. multivorans OMP 为基础的疫苗在小鼠中成功产生了保护性免疫反应。在这里,我们使用新型黏膜佐剂(纳米乳剂)和新型 B. cenocepacia 基于 OMP 的抗原来评估针对 Bcc 的实验性黏膜疫苗。源自 B. cenocepacia 的 OMP 抗原与纳米乳剂或 PBS 混合,并通过鼻腔内给药给 CD-1 小鼠。血清分析显示,与对照小鼠相比,接种疫苗的小鼠产生了强大的 IgG 和黏膜分泌型 IgA 免疫反应。这些抗体对 B. cenocepacia 和 B. multivorans 物种均具有交叉中和活性。我们发现,免疫接种的小鼠对 B. cenocepacia 的肺部定植具有保护作用。我们还发现,在黏膜免疫接种中,一种在伯克霍尔德菌和罗尔斯顿菌属之间高度保守的 17 kDa OmpA 样蛋白是一种新的免疫显性表位。

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