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用新凶手弗朗西斯菌U112进行亚致死感染的小鼠,对强毒A型或B型土拉弗朗西斯菌的全身或气溶胶攻击仅产生微弱的保护性免疫。

Mice sublethally infected with Francisella novicida U112 develop only marginal protective immunity against systemic or aerosol challenge with virulent type A or B strains of F. tularensis.

作者信息

Shen Hua, Chen Wangxue, Conlan J Wayne

机构信息

National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Room 3065 Ottawa, Ont., Canada K1A OR6.

出版信息

Microb Pathog. 2004 Aug;37(2):107-10. doi: 10.1016/j.micpath.2004.04.005.

DOI:10.1016/j.micpath.2004.04.005
PMID:15312850
Abstract

The current study determined the ability of Francisella novicida to act as a live vaccine against the much more virulent, but closely related pathogen, Francisella tularensis. Live attenuated strains of the latter are effective vaccines against human tularemia. However, the molecular cause of their attenuation remains unknown, and this is a regulatory barrier for licensing such vaccines. Moreover, F. tularensis is exceptionally difficult to manipulate genetically. This is hampering the development of rationally attenuated vaccine strains. F. novicida shares a lot of genetic homology with F. tularensis and is more amenable to genetic manipulation. If the former naturally expresses the protective antigens of the latter, it could be used to develop a defined tularemia vaccine. However, the results presented herein show that wild-type F. novicida elicits almost no protection in mice against challenge with virulent F. tularensis.

摘要

当前的研究确定了新凶手弗朗西斯菌作为一种活疫苗,抵抗毒性更强但亲缘关系密切的病原体——土拉热弗朗西斯菌的能力。后者的减毒活菌株是预防人类兔热病的有效疫苗。然而,其减毒的分子原因仍然未知,这是此类疫苗获批的一个监管障碍。此外,土拉热弗朗西斯菌极难进行基因操作。这阻碍了合理减毒疫苗株的开发。新凶手弗朗西斯菌与土拉热弗朗西斯菌有许多基因同源性,并且更易于进行基因操作。如果前者能天然表达后者的保护性抗原,那么它可用于开发一种明确的兔热病疫苗。然而,本文给出的结果表明,野生型新凶手弗朗西斯菌在小鼠中几乎不能诱导出抵抗强毒土拉热弗朗西斯菌攻击的保护作用。

相似文献

1
Mice sublethally infected with Francisella novicida U112 develop only marginal protective immunity against systemic or aerosol challenge with virulent type A or B strains of F. tularensis.用新凶手弗朗西斯菌U112进行亚致死感染的小鼠,对强毒A型或B型土拉弗朗西斯菌的全身或气溶胶攻击仅产生微弱的保护性免疫。
Microb Pathog. 2004 Aug;37(2):107-10. doi: 10.1016/j.micpath.2004.04.005.
2
Tularemia in BALB/c and C57BL/6 mice vaccinated with Francisella tularensis LVS and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background.用土拉弗朗西斯菌活疫苗株(LVS)接种的BALB/c和C57BL/6小鼠,经皮内注射或通过气溶胶暴露于该病原体的强毒株进行攻毒:保护效果因病原体毒力、暴露途径和宿主遗传背景而异。
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3
Aerosol-, but not intradermal-immunization with the live vaccine strain of Francisella tularensis protects mice against subsequent aerosol challenge with a highly virulent type A strain of the pathogen by an alphabeta T cell- and interferon gamma- dependent mechanism.用土拉弗朗西斯菌活疫苗株进行气溶胶免疫(而非皮内免疫),可通过αβ T细胞和γ干扰素依赖机制,保护小鼠免受该病原体高毒力A型菌株随后的气溶胶攻击。
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Differential ability of novel attenuated targeted deletion mutants of Francisella tularensis subspecies tularensis strain SCHU S4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization.新型减毒靶向缺失突变株弗朗西斯氏菌亚种土拉弗朗西斯菌 SCHU S4 对小鼠气溶胶攻毒的保护作用不同:宿主背景和免疫途径的影响。
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Interleukin-17 protects against the Francisella tularensis live vaccine strain but not against a virulent F. tularensis type A strain.白细胞介素-17 可预防 弗氏柠檬酸杆菌活疫苗株,但不能预防毒力强的弗氏柠檬酸杆菌 A 型菌株。
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Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (DeltaiglB) induces protective immunity against homotypic and heterotypic challenge.用特定的土拉弗朗西斯菌新凶手亚种致病岛突变体(ΔiglB)进行疫苗接种可诱导针对同型和异型攻击的保护性免疫。
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A Francisella tularensis live vaccine strain (LVS) mutant with a deletion in capB, encoding a putative capsular biosynthesis protein, is significantly more attenuated than LVS yet induces potent protective immunity in mice against F. tularensis challenge.一株编码一种假定荚膜生物合成蛋白的 capB 缺失的活疫苗弗朗西斯氏菌(LVS)突变体比 LVS 显著减毒,但能诱导小鼠对弗朗西斯氏菌挑战产生强烈的保护性免疫。
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引用本文的文献

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Development, Strategies, and Challenges for Tularemia Vaccine.土拉菌病疫苗的研发、策略及挑战。
Curr Microbiol. 2024 Apr 2;81(5):126. doi: 10.1007/s00284-024-03658-0.
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Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent subsp. .减毒活土拉弗朗西丝菌疫苗对呼吸道感染强毒. 亚种的保护作用。
Front Cell Infect Microbiol. 2018 May 15;8:154. doi: 10.3389/fcimb.2018.00154. eCollection 2018.
3
Comparative phosphoproteomics reveals components of host cell invasion and post-transcriptional regulation during Francisella infection.
比较磷酸蛋白质组学揭示了弗朗西斯菌感染过程中宿主细胞入侵和转录后调控的组成部分。
Mol Cell Proteomics. 2013 Nov;12(11):3297-309. doi: 10.1074/mcp.M113.029850. Epub 2013 Aug 22.
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Current status of vaccine development for tularemia preparedness.用于土拉菌病防范的疫苗研发现状。
Clin Exp Vaccine Res. 2013 Jan;2(1):34-9. doi: 10.7774/cevr.2013.2.1.34. Epub 2013 Jan 15.
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Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development.迈向未来:对土拉弗朗西斯菌发病机制和疫苗开发的洞察。
Microbiol Mol Biol Rev. 2009 Dec;73(4):684-711. doi: 10.1128/MMBR.00028-09.
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Rationally designed tularemia vaccines.合理设计的兔热病疫苗。
Expert Rev Vaccines. 2009 Jul;8(7):877-85. doi: 10.1586/erv.09.51.
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Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia.给予合成的Toll样受体4(TLR4)激动剂可保护小鼠免受肺型兔热病感染。
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Identification of immunologic and pathologic parameters of death versus survival in respiratory tularemia.呼吸型兔热病死亡与存活的免疫和病理参数鉴定
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Identification of an orphan response regulator required for the virulence of Francisella spp. and transcription of pathogenicity island genes.鉴定一种弗氏杆菌属毒力及致病岛基因转录所需的孤儿应答调节因子。
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The immunologically distinct O antigens from Francisella tularensis subspecies tularensis and Francisella novicida are both virulence determinants and protective antigens.来自土拉弗朗西斯菌土拉亚种和新凶手弗朗西斯菌的免疫特性不同的O抗原既是毒力决定因素,也是保护性抗原。
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