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用于诱导HIV特异性黏膜和全身免疫反应的活口服沙门氏菌-HIV-1疫苗载体的优化

Optimization of live oral Salmonella-HIV-1 vaccine vectors for the induction of HIV-specific mucosal and systemic immune responses.

作者信息

Hone D M, Wu S, Powell R J, Pascual D W, Van Cott J, McGhee J, Fouts T R, Tuskan R G, Lewis G K

机构信息

Vaccine Vector Group, School of Medicine, University of Maryland at Baltimore, USA.

出版信息

J Biotechnol. 1996 Jan 26;44(1-3):203-7. doi: 10.1016/0168-1656(95)00151-4.

DOI:10.1016/0168-1656(95)00151-4
PMID:8717405
Abstract

Recent evidence suggests that live oral Salmonella-HIV vaccine vectors have the potential to elicit HIV-specific T cell-mediated immunity in both the mucosal and systemic compartments. We are using the mouse-typhoid model to identify Salmonella::HIV vaccine vector constructs that elicit HIV-specific mucosal and systemic immune responses. Oral immunization of mice with a Salmonella strain that expresses recombinant gp120 (rgp120) in the cytoplasm of the vector elicits a modest gp120-specific T cell proliferation response in the spleen. However, such Salmonella constructs did not stimulate the development of gp120-specific serum IgG or cytotoxic T lymphocytes (CTLs). Interestingly, the majority of cytoplasmically-expressed rgp120 forms inclusion bodies in Salmonella. We believe that in this form rgp120 is highly susceptible to protease degradation by the vector. As such, cytoplasmic rgp120 may not persist in the host after vaccination, resulting in the modest immunogenicity of rgp120 in these constructs. To circumvent this problem we constructed Salmonella strains that express rgp120 on the surface of the vector. Preliminary data suggest that surface-expressed rgp120 is significantly more immunogenic in both the mucosal and systemic compartments than cytoplasmic rgp120. These results, therefore, support the proposal that Salmonella vectors will be a safe and inexpensive means for delivery of HIV antigens to, and the elicitation of HIV-specific T cells in, the mucosal and systemic compartments.

摘要

近期证据表明,口服活的沙门氏菌 - HIV疫苗载体有潜力在黏膜和全身 compartments 中引发HIV特异性T细胞介导的免疫反应。我们正在使用小鼠伤寒模型来鉴定能引发HIV特异性黏膜和全身免疫反应的沙门氏菌::HIV疫苗载体构建体。用在载体细胞质中表达重组gp120(rgp120)的沙门氏菌菌株口服免疫小鼠,可在脾脏中引发适度的gp120特异性T细胞增殖反应。然而,这种沙门氏菌构建体并未刺激gp120特异性血清IgG或细胞毒性T淋巴细胞(CTL)的发育。有趣的是,大多数在细胞质中表达的rgp120在沙门氏菌中形成包涵体。我们认为,以这种形式存在的rgp120极易受到载体蛋白酶降解的影响。因此,细胞质中的rgp120在接种疫苗后可能无法在宿主体内持续存在,导致这些构建体中rgp120的免疫原性较低。为了解决这个问题,我们构建了在载体表面表达rgp120的沙门氏菌菌株。初步数据表明,表面表达的rgp120在黏膜和全身 compartments 中的免疫原性明显高于细胞质中的rgp120。因此,这些结果支持了以下提议,即沙门氏菌载体将是一种安全且廉价的手段,用于将HIV抗原递送至黏膜和全身 compartments 并在其中引发HIV特异性T细胞。

注

原文中“compartments”可能是“compartments”拼写错误,结合语境推测可能是“compartments”,意为“区室”,这里统一翻译为“compartments” ,你可根据实际情况调整。

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