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重组 FimH,即副溶血性弧菌菌毛顶端黏附素,可引发混合 T 辅助细胞应答,并在鼠模型中赋予针对副溶血性弧菌攻击的保护作用。

Recombinant FimH, a fimbrial tip adhesin of Vibrio parahaemolyticus, elicits mixed T helper cell response and confers protection against Vibrio parahaemolyticus challenge in murine model.

机构信息

School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.

Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India.

出版信息

Mol Immunol. 2021 Jul;135:373-387. doi: 10.1016/j.molimm.2021.05.005. Epub 2021 May 18.

DOI:10.1016/j.molimm.2021.05.005
PMID:34020083
Abstract

Vibrio parahaemolyticus causes vibriosis in wide range of marine organisms, and is responsible for food borne illnesses in humans through consumption of contaminated uncooked/partially cooked seafood. Continued and widespread antibiotics usage to increase the productivity has led to antibiotics resistance development. This has necessitated the need to develop alternative methods to control its infection. Use of safe and effective vaccines against the virulence factors not only protects from infection, it also minimizes antibiotic usage. The colonization of V. parahaemolyticus in the host and disease development requires several adhesins present on the cell surface, and thereby make them attractive vaccine candidates. V. parahaemolyticus produces extracellular type 1 fimbriae that have been shown to play a role in adhesion, biofilm formation and virulence. FimH is one of the minor components of the type 1 fimbriae occurring on its very tip. Being present on the cell surface, it is highly immunogenic, and can be targeted as a potential vaccine candidate. The present study describes the immunogenic and vaccine potential of recombinant V. parahaemolyticus FimH (rVpFimH) expressed in E. coli. Immunization of BALB/c mice with the rVpFimH elicited a strong mixed immune response, T-cell memory (evidenced by antibody isotyping, cytokine profiling and T-cell proliferation assay), and agglutination positive antibodies. FACS analysis and immunogold labeling showed that the polyclonal anti-rVpFimH antibodies were able to recognize the FimH on V. parahaemolyticus cells. In vivo challenge of the rVpFimH-immunized mice with 2×LD dose of live bacteria showed one hundred percent survival. Thus, our findings clearly demonstrate the potential of FimH as an effective vaccine candidate against V. parahaemolyticus.

摘要

副溶血性弧菌可引起多种海洋生物的弧菌病,并可通过食用受污染的未煮熟/未煮熟的海鲜导致食源性疾病。为了提高生产力,人们持续广泛地使用抗生素,导致了抗生素耐药性的发展。这就需要开发替代方法来控制其感染。使用针对毒力因子的安全有效的疫苗不仅可以预防感染,还可以最大限度地减少抗生素的使用。副溶血性弧菌在宿主中的定植和疾病发展需要其细胞表面存在几种黏附素,因此它们成为有吸引力的疫苗候选物。副溶血性弧菌产生细胞外 1 型菌毛,这些菌毛已被证明在黏附、生物膜形成和毒力中起作用。FimH 是 1 型菌毛的次要成分之一,存在于其顶端。由于存在于细胞表面,它具有高度的免疫原性,可以作为一种潜在的疫苗候选物。本研究描述了在大肠杆菌中表达的重组副溶血性弧菌 FimH(rVpFimH)的免疫原性和疫苗潜力。用 rVpFimH 免疫 BALB/c 小鼠可引发强烈的混合免疫反应、T 细胞记忆(通过抗体分型、细胞因子分析和 T 细胞增殖试验证实)和凝集阳性抗体。FACS 分析和免疫金标记显示,多克隆抗 rVpFimH 抗体能够识别副溶血性弧菌细胞上的 FimH。用 2×LD 剂量的活细菌对 rVpFimH 免疫的小鼠进行体内攻毒试验,结果显示 100%存活。因此,我们的研究结果清楚地表明,FimH 作为一种有效的副溶血性弧菌疫苗候选物具有潜力。

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