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用侵袭性递送的假定丝氨酸蛋白酶和小鼠白细胞介素-4 DNA对小鼠进行口服疫苗接种可引发保护性免疫。

Oral Vaccination of Mice With Putative Serine Protease and Murine Interleukin-4 DNA Delivered by Invasive Elicits Protective Immunity.

作者信息

Xue Ying, Zhang Bo, Wang Nan, Huang Hai-Bin, Quan Yu, Lu Hui-Nan, Zhu Zhi-Yu, Li Jun-Yi, Pan Tian-Xu, Tang Yue, Jiang Yan-Long, Shi Chun-Wei, Yang Gui-Lian, Wang Chun-Feng

机构信息

College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.

Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China.

出版信息

Front Microbiol. 2022 May 3;13:859243. doi: 10.3389/fmicb.2022.859243. eCollection 2022.

Abstract

Trichinellosis is a serious zoonotic parasitic disease caused by () that causes considerable economic losses for the global pig breeding and food industries. As such, there is an urgent need for a vaccine that can prevent infection. Previous studies have reported that recombinant invasive (LL) expressing fibronectin binding protein A (LL-FnBPA+) can transfer DNA vaccines directly to dendritic cells (DCs) across an epithelial cell monolayer, leading to significantly higher amounts of heterologous protein expression compared to non-invasive . In this study, the invasive bacterium () expressing FnBPA was used as a carrier to deliver a novel oral DNA vaccine consisting of adult putative serine protease (Ts-ADpsp) and murine interleukin (IL)-4 DNA to mouse intestinal epithelial cells. Experimental mice were orally immunized 3 times at 10-day intervals. At 10 days after the last vaccination, mice were challenged with 350 infective larvae by oral inoculation. Immunization with invasive harboring pValac-Ts-ADpsp/pSIP409-FnBPA induced the production of anti-Ts-ADpsp-specific IgG of serum, type 1 and 2 helper T cell cytokines of mesenteric lymph node (MLN) and spleen, secreted (s) IgA of intestinal lavage, and decreased burden and intestinal damage compared to immunization with non-invasive expressing Ts-ADpsp (pValac-Ts-ADpsp/pSIP409). Thus, invasive expressing FnBPA and IL-4 stimulates both mucosal and cellular immune response to protect against infection, highlighting its therapeutic potential as an effective DNA vaccine for trichinellosis.

摘要

旋毛虫病是一种由()引起的严重人畜共患寄生虫病,给全球养猪业和食品工业造成了相当大的经济损失。因此,迫切需要一种能够预防感染的疫苗。先前的研究报道,表达纤连蛋白结合蛋白A的重组侵袭性(LL)(LL-FnBPA+)可以通过上皮细胞单层将DNA疫苗直接转移到树突状细胞(DCs),与非侵袭性()相比,导致更高量的异源蛋白表达。在本研究中,表达FnBPA的侵袭性细菌()被用作载体,将一种由旋毛虫成虫推定丝氨酸蛋白酶(Ts-ADpsp)和小鼠白细胞介素(IL)-4 DNA组成的新型口服DNA疫苗递送至小鼠肠道上皮细胞。实验小鼠每隔10天口服免疫3次。在最后一次接种疫苗后10天,通过口服接种用350条感染性幼虫对小鼠进行攻击。与用表达Ts-ADpsp的非侵袭性(pValac-Ts-ADpsp/pSIP409)免疫相比,用携带pValac-Ts-ADpsp/pSIP409-FnBPA的侵袭性()免疫诱导了血清中抗Ts-ADpsp特异性IgG、肠系膜淋巴结(MLN)和脾脏中1型和2型辅助性T细胞细胞因子、肠道灌洗液中分泌型(s)IgA的产生,并减轻了()负担和肠道损伤。因此,表达FnBPA和IL-4的侵袭性()刺激黏膜和细胞免疫反应以预防()感染,突出了其作为旋毛虫病有效DNA疫苗的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0d/9113538/23a59dde6e5e/fmicb-13-859243-g001.jpg

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