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用多杀性巴氏杆菌重组外膜蛋白A进行疫苗接种会在小鼠体内诱导强烈但无保护作用且有害的Th2型免疫反应。

Vaccination with Pasteurella multocida recombinant OmpA induces strong but non-protective and deleterious Th2-type immune response in mice.

作者信息

Dabo S Mady, Confer Anthony, Montelongo Marie, York Petrina, Wyckoff John H

机构信息

Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078-2007, USA.

出版信息

Vaccine. 2008 Aug 12;26(34):4345-51. doi: 10.1016/j.vaccine.2008.06.029. Epub 2008 Jul 1.

Abstract

Pasteurella multocida OmpA (PmOmpA) belongs to the major and multifunctional Escherichia coli OmpA family of proteins. We have previously reported that the protein is conserved, immunogenic and an adhesin that binds host cells and host cell extracellular matrix molecules [Dabo SM, Confer AW, Quijano-Blas RA. Molecular and immunological characterization of Pasteurella multocida serotype A:3 OmpA: evidence of its role in P. multocida interaction with extracellular matrix molecules. Microb Pathog 2003;35(4):147-157]. In this study, we found that immunization of mice with the recombinant PmOmpA elicited strong Th2-type immune response, characterized by high immunoglobulin G(1) (IgG(1)) antibodies production. Subsequent intraperitoneal homologous challenge of the immunized mice resulted in lack of protection associated with the high IgG(1) titers in anti-rPmOmpA sera. Furthermore, the protection afforded by vaccination with P. multocida OMPs alone was adversely affected by the addition of the rPmOmpA to the vaccine preparations. The results demonstrate that PmOmpA has a detrimental effect on the efficacy of vaccination with OMPs in mice. Targeted inactivation of pmOmpA gene in P. multocida 232 represents a potential mean towards the development of an effective vaccine candidate.

摘要

多杀性巴氏杆菌外膜蛋白A(PmOmpA)属于大肠杆菌主要多功能外膜蛋白A家族。我们之前报道过该蛋白具有保守性、免疫原性,是一种能结合宿主细胞和宿主细胞外基质分子的黏附素[Dabo SM,Confer AW,Quijano-Blas RA。多杀性巴氏杆菌A:3血清型OmpA的分子和免疫学特性:其在多杀性巴氏杆菌与细胞外基质分子相互作用中作用的证据。微生物病原体2003;35(4):147 - 157]。在本研究中,我们发现用重组PmOmpA免疫小鼠可引发强烈的Th2型免疫反应,其特征是产生高免疫球蛋白G(1)(IgG(1))抗体。随后对免疫小鼠进行腹腔内同源攻击,结果显示缺乏保护作用,且抗rPmOmpA血清中IgG(1)滴度较高。此外,在疫苗制剂中添加rPmOmpA会对单独使用多杀性巴氏杆菌外膜蛋白(OMPs)进行疫苗接种所提供的保护产生不利影响。结果表明,PmOmpA对小鼠OMPs疫苗接种效果具有有害作用。在多杀性巴氏杆菌232中对pmOmpA基因进行靶向失活是开发有效候选疫苗的一种潜在手段。

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