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