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

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
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DOI:
10.1007/s00430-009-0137-2
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发表时间:
2010-05-01
影响因子:
5.4
通讯作者:
Baker, J. R., Jr.
Baker, J. R., Jr.
中科院分区:
医学2区
文献类型:
--
作者:
Makidon, P. E.;Knowlton, J.;Baker, J. R., Jr.

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洋葱伯克霍尔德菌复合体(BCC)是与囊性纤维化患者的危及生命的疾病相关的机会性细菌。一旦Bcc定殖建立,这些抗微生物剂抗性和生物膜形成细菌就难以根除,并且与发病率和死亡率增加有关。目前,没有疫苗可以预防Bcc感染。目前,关于预防伯克霍尔德菌定植的疫苗开发的公开信息很少。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在小鼠中产生了成功的保护性免疫应答。基于多噬菌体OMP的疫苗。在这里,我们评估了一种实验性的粘膜疫苗对BCC使用一种新的粘膜佐剂(纳米乳液)和一种新的B。基于新洋葱的OMP抗原。OMP抗原来源于B。将新洋葱与纳米乳液或PBS混合,并鼻内递送至CD-1小鼠。血清分析显示,与对照小鼠相比,接种疫苗的小鼠具有稳健的IgG和粘膜分泌型伊加免疫应答。抗体对两种B都具有交叉中和活性。cenocepacia和B.多食种类。我们发现免疫小鼠对B的肺定植有保护作用。cenocepacia。我们还确定了一个17 kDa的OmPA样蛋白高度保守的伯克霍尔德菌和罗尔斯通氏菌物种之间作为一个新的免疫显性表位在粘膜免疫。
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.