口服表达 Nudix 水解酶和 43 kDa 蛋白的重组植物乳杆菌对 BALB/c 小鼠旋毛虫感染的保护作用。
Oral immunization with recombinant Lactobacillus plantarum expressing Nudix hydrolase and 43 kDa proteins confers protection against Trichinella spiralis in BALB/c mice.
机构信息
College of Veterinary Medicine, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China; Key Laboratory of animal production and product quality safety of Ministry of Education, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China.
College of Veterinary Medicine, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China; Key Laboratory of animal production and product quality safety of Ministry of Education, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin Province 130118, China; College of Food Engineering, Jilin Engineering Normal University, Changchun, Jilin 130052, China.
出版信息
Acta Trop. 2021 Aug;220:105947. doi: 10.1016/j.actatropica.2021.105947. Epub 2021 May 7.
Trichinellosis is a significant food-borne zoonotic parasitic disease caused by parasite Trichinella. Given the side effects of anti-Trichinella drugs (e.g., Mebendazole) aroused in the course of treatments, an effective vaccine against the parasite is called for. The therapies available to date are in most instances targeting a single stage of Trichinella, resulting in an incomplete protective immunity against the parasite in terms of the complexity of its developmental stages. In this study, a recombinant dual-expression double anchor vector NC8-pLp-TsNd-S-pgsA'-gp43 was constructed carrying two antigen genes from Trichinella spiralis (T. spiralis), encoding the gp43 and T. spiralis Nudix hydrolase (TsNd) proteins which were mainly expressed in muscle larva (ML) and intestinal infective larva stages of the parasite respectively. These two proteins were to be expressed by Lactobacillus plantarum NC8 (L. plantarum NC8) which was designed to express the two anchored peptides, a truncated poly-γ-glutamic acid synthetase A (pgsA') and the surface layer protein of Lactobacillus acidophilus (SlpA), on its surface for attaching expressed foreign proteins. Oral immunization with the above recombinant vaccine induced higher levels of specific serum IgG and mucosal secretory IgA (SIgA) in BALB/c mice. In addition, cytokines, interferon-γ (IFN- γ), interleukin-4 (IL-4) and IL-17 released by lymphocytes, and CD4 levels displayed on the surfaces of splenic and mesenteric lymph cells were significantly enhanced by the vaccination. Moreover, after larval challenges, a 75.67 % reduction of adult worms (AW) at 7 days post-infection (dpi) and 57.14 % reduction of ML at 42 dpi were observed in mice immunized with the recombinant vaccine. Furthermore, this oral vaccination reduced the counts of encysted larvae presented in tongue and masseter muscles after infected with T. spiralis in mice. The overall results demonstrated that the recombinant vaccine developed in this study could induce specific humoral, mucosal, and cellular immune responses, and provides protections against different stages (adult worms and muscle larva) of T. spiralis infections in BALB/c mice, which could make it a promising oral vaccine candidate against trichinellosis.
旋毛虫病是一种由寄生虫旋毛虫引起的重要食源性人畜共患寄生虫病。鉴于抗旋毛虫药物（如苯并咪唑）在治疗过程中引起的副作用，人们呼吁开发一种有效的寄生虫疫苗。迄今为止，可用的疗法在大多数情况下都针对旋毛虫的单一阶段，导致针对寄生虫发育阶段的复杂性的不完全保护性免疫。在这项研究中，构建了一种携带旋毛虫（T. spiralis）两个抗原基因的重组双表达双锚定载体 NC8-pLp-TsNd-S-pgsA'-gp43，分别编码 gp43 和 T. spiralis Nudix 水解酶（TsNd）蛋白，这些蛋白主要在寄生虫的肌肉幼虫（ML）和肠感染幼虫阶段表达。这两种蛋白将由植物乳杆菌 NC8（L. plantarum NC8）表达，该菌设计用于表达两个锚定肽，即截短的多聚γ-谷氨酸合成酶 A（pgsA'）和嗜酸乳杆菌的表面层蛋白（SlpA），用于附着表达的外源蛋白。口服免疫上述重组疫苗可诱导 BALB/c 小鼠产生更高水平的特异性血清 IgG 和黏膜分泌型 IgA（SIgA）。此外，淋巴细胞释放的细胞因子干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）和白细胞介素-17 以及脾和肠系膜淋巴细胞表面的 CD4 水平也显著增强。此外，在幼虫攻毒后，感染重组疫苗的小鼠在感染后 7 天（dpi）成虫（AW）减少 75.67%，42 天肌肉幼虫（ML）减少 57.14%。此外，该口服疫苗可减少感染旋毛虫的小鼠舌和咀嚼肌中包囊幼虫的数量。总的来说，本研究开发的重组疫苗能够诱导特异性体液、黏膜和细胞免疫应答，并为 BALB/c 小鼠提供针对旋毛虫不同阶段（成虫和肌肉幼虫）感染的保护作用，使其成为一种有前途的抗旋毛虫病口服疫苗候选物。
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