Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.
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DOI:
10.1371/journal.pone.0107180
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Vemulapalli R
Vemulapalli R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dabral N;Martha-Moreno-Lafont;Sriranganathan N;Vemulapalli R

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布鲁氏菌属是革兰氏阴性、兼性细胞内球杆菌,引起世界上最常见的人畜共患病之一。人类通过食用受污染的乳制品和肉制品以及直接接触流产的动物组织和体液自然而然地受到感染。没有可用于人类的布鲁氏菌病疫苗。在这项研究中,我们测试了口服接种的经伽马射线照射的流产芽胞杆菌和流产芽孢杆菌 RB51 在初免-加强免疫方法中诱导抗原特异性体液和细胞介导的免疫以及针对强毒流产芽孢杆菌 2308 攻击的保护能力。用流产芽孢杆菌 RB51 和流产芽胞杆菌 RB51 进行异源初免加强疫苗接种以及同源初免加强疫苗接种 感染瘤芽孢杆菌的小鼠导致产生针对平滑脂多糖的特异性血清和粘膜抗体。引发的血清抗体包括 IgM、IgG1、IgG2a、IgG2b 和 IgG3 同种型。所有口服疫苗方案均诱导能够分泌 IFN-γ 和 TNF-α 的抗原特异性 CD4+ 和 CD8+ T 细胞。腹膜内攻击后,接种新生芽孢杆菌的小鼠对脾脏和肝脏中有毒的流产芽孢杆菌 2308 定植表现出最高水平的抵抗力。使用不同剂量的新芽孢杆菌进行的实验表明,所有测试剂量的 109、1010 和 1011 CFU 当量均能显着防止腹膜内攻击。然而,需要 1011 CFU 当量的 B. neotomae 剂量才能提供针对鼻内攻击的保护,如脾和肺中细菌定植减少所示。总而言之,这些结果证明了使用伽马射线照射的新芽孢杆菌作为有效且安全的口服疫苗来诱导预防有毒布鲁氏菌呼吸道和全身感染的可行性。
Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4+ and CD8+ T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 109, 1010 and 1011 CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 1011 CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.
DOI: 10.1371/journal.pone.0002760
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DOI: 10.1128/iai.01787-05
发表时间: 2006-07-01
影响因子: 3.1
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Kahl-McDonagh, M. M.;Ficht, T. A.
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DOI: 10.1093/clinids/21.2.283
发表时间: 1995-08-01
影响因子: 11.8
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DOI: 10.4049/jimmunol.1302561
发表时间: 2014-04-15
影响因子: 4.4
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Vitry, Marie-Alice;Mambres, Delphine Hanot;Muraille, Eric
通讯作者: Muraille, Eric
DOI: 10.1128/cdli.12.12.1429-1436.2005
发表时间: 2005-12-01
期刊: CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子: --
作者:
Sanakkayala, N;Sokolovska, A;Vemulapalli, R
通讯作者: Vemulapalli, R