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Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus

机译:靶向肠道微折叠细胞和树突状细胞的口服重组乳杆菌疫苗,用于递送猪流行性腹泻病毒的核心中和表位

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Porcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) has led to serious economic losses to the swine industry worldwide. In this study, an oral recombinant Lactobacillus casei vaccine against PEDV infection targeting the intestinal microfold (M) cells and dendritic cells (DCs) for delivering the core neutralizing epitope (COE) of PEDV spike protein was developed with M cell-targeting peptide (Col) and dendritic cell-targeting peptide (DCpep). The immunogenicity of the orally administered recombinant strains was evaluated. After immunization, significantly higher levels of anti-PEDV specific IgG antibodies with PEDV neutralizing activity in the sera and mucosal sIgA antibodies in the tractus genitalis, intestinal mucus, and stools were detected in mice orally administered with the recombinant strain pPG-COE-Col-DCpep/L393, which expressed DCpep and Col targeting ligands fused with the PEDV COE antigen, compared to mice orally immunized with the recombinant strain pPG-COE/L393 without the DCpep and Col targeting ligands. Moreover, in response to restimulation with the PEDV COE antigen in vitro, a significant difference in splenocyte proliferation response and Th2-associated cytokine IL-4 level was observed in the group of mice orally immunized with pPG-COE-Col-DCpep/L393 (p?
机译:由猪流行性腹泻病毒(PEDV)引起的猪流行性腹泻已导致全世界养猪业的严重经济损失。在这项研究中,针对M靶向肽(Col)的针对PEDV感染的肠道重组干酪乳杆菌疫苗开发了针对肠道微褶(M)细胞和树突细胞(DC)的PEDV刺突蛋白核心核心中和表位(COE)的递送。 )和树突状细胞靶向肽(DCpep)。评价了口服施用的重组菌株的免疫原性。免疫后,口服重组质粒pPG-COE-Col-与用无DCpep和Col靶向配体的重组品系pPG-COE / L393口服免疫的小鼠相比,表达与PEDV COE抗原融合的DCpep和Col靶向配体的DCpep / L393。此外,在体外用PEDV COE抗原进行再刺激时,在经pPG-COE-Col-DCpep / L393口服免疫的小鼠中,脾细胞增殖反应和Th2相关细胞因子IL-4水平存在显着差异(与分别接受pPG-COE-Col / L393和pPG-COE-DCpep / L393的小鼠组相比,p≥0.05。表达PEDV的COE抗原的基因工程乳杆菌的靶向肠道M细胞和DCs的口服给药可通过口服给药有效诱导抗PEDV的粘膜,体液和细胞免疫反应,这表明针对PEDV感染的疫苗策略很有希望。

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