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用表达流产布鲁氏菌翻译起始因子3的重组塞姆利基森林病毒颗粒进行疫苗接种可诱导BALB/c小鼠产生保护性免疫。

Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice.

作者信息

Cabrera Alex, Sáez Darwin, Céspedes Sandra, Andrews Edilia, Oñate Angel

机构信息

Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Chile.

出版信息

Immunobiology. 2009;214(6):467-74. doi: 10.1016/j.imbio.2008.11.016. Epub 2009 Jan 17.

Abstract

Recombinant replicons of Semliki Forest virus (SFV) can be used to induce high-level, transient expression of heterologous proteins in vivo. We constructed infectious but replication-deficient SFV particles carrying recombinant RNA encoding the Brucella abortus translation initiation factor 3 (IF3). The recombinant SFV particles (SFV-IF3 particles) were then evaluated for their ability to induce immune responses and to protect BALB/c mice against a challenge with B. abortus 2308 following vaccination. Animals inoculated with SFV-IF3 developed IF3-specific IgM antibodies at day 14 post-immunization. In vitro stimulation of splenocytes from vaccinated mice with either recombinant IF3 (rIF3) or crude Brucella protein extracts resulted in a T-cell proliferative response and induction of interferon gamma secretion, but not interleukin-4. In addition, mice immunized with SFV-IF3 exhibited a significant level of resistance against challenge with the virulent B. abortus strain 2308 (P<0.01). These findings indicate that an SFV-based vector carrying RNA encoding Brucella IF3 has potential for use as a vaccine to induce protection against B. abortus infections.

摘要

塞姆利基森林病毒(SFV)的重组复制子可用于在体内诱导异源蛋白的高水平瞬时表达。我们构建了携带编码流产布鲁氏菌翻译起始因子3(IF3)的重组RNA的感染性但复制缺陷型SFV颗粒。然后评估重组SFV颗粒(SFV-IF3颗粒)在接种疫苗后诱导免疫反应以及保护BALB/c小鼠免受流产布鲁氏菌2308攻击的能力。接种SFV-IF3的动物在免疫后第14天产生了IF3特异性IgM抗体。用重组IF3(rIF3)或粗制布鲁氏菌蛋白提取物体外刺激接种疫苗小鼠的脾细胞,会导致T细胞增殖反应并诱导γ干扰素分泌,但不会诱导白细胞介素-4分泌。此外,用SFV-IF3免疫的小鼠对强毒流产布鲁氏菌菌株2308的攻击表现出显著的抵抗力(P<0.01)。这些发现表明,携带编码布鲁氏菌IF3的RNA的基于SFV的载体有潜力用作疫苗来诱导针对流产布鲁氏菌感染的保护作用。

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