Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus.
Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus.
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口服重组乳杆菌疫苗靶向肠道微褶皱细胞和树突状细胞，传递猪流行性腹泻病毒的核心中和表位
DOI：
10.1186/s12934-018-0861-7
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发表时间：
2018-02-09
影响因子：
6.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Ma S;Wang L;Huang X;Wang X;Chen S;Shi W;Qiao X;Jiang Y;Tang L;Xu Y;Li Y
背景：由猪流行性腹泻病毒（PEDV）引起的猪流行性腹泻给世界养猪业造成了严重的经济损失。本研究以PEDV刺突蛋白的核心中和表位（COE）为靶点，以肠道微褶细胞（M）和树突状细胞（DC）为靶点，利用M细胞靶向肽（Col）和树突状细胞靶向肽（DCpep）构建了口服重组干酪乳杆菌疫苗。结果：免疫后，与用不含DCpep和Col靶向配体的重组菌株pPG-COE/L393口服免疫的小鼠相比，在口服施用表达与PEDV COE抗原融合的DCpep和Col靶向配体的重组菌株pPG-COE-Col-DCpep/L393的小鼠中检测到血清中具有PEDV中和活性的抗PEDV特异性IgG抗体和生殖道、肠粘液和粪便中的粘膜sIgA抗体的显著更高水平。此外，在对体外用PEDV COE抗原再刺激的应答中，在用pPG-COE-Col-DCpep/L393口服免疫的小鼠组中观察到脾细胞增殖应答和Th 2相关细胞因子IL-4水平的显著差异与分别接受pPG-COE-Col/L393和pPG-COE-DCpep/L393的小鼠组相比，pPG-COE-Col/L393和pPG-COE-DCpep/L393的小鼠组具有更高的细胞增殖率（p < 0.05）。表达PEDV的COE抗原的基因工程乳杆菌的肠M细胞和DC靶向口服递送可以通过口服施用有效地诱导抗PEDV粘膜、体液和细胞免疫应答，表明针对PEDV感染的有希望的疫苗策略。
Background: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.Results: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 < 0.05) compared to the groups of mice that received pPG-COE-Col/L393 and pPG-COE-DCpep/L393, respectively.Conclusions:The intestinal M cells- and DCs-targeting oral delivery of genetically engineered Lactobacillus expressing the COE antigen of PEDV can efficiently induce anti-PEDV mucosal, humoral, and cellular immune responses via oral administration, suggesting a promising vaccine strategy against PEDV infection.
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DOI：
10.4049/jimmunol.1601775
发表时间：
2017-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boyaka PN
通讯作者：
Boyaka PN
影响因子：
2.7
作者：
Kim H;Lee YK;Kang SC;Han BK;Choi KM
通讯作者：
Choi KM
DOI：
10.1073/pnas.0500098102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Mohamadzadeh, M;Olson, S;Klaenhammer, TR
通讯作者：
Klaenhammer, TR
影响因子：
4.4
作者：
Kim, Sae-Hae;Seo, Ki-Weon;Jang, Yong-Suk
通讯作者：
Jang, Yong-Suk
影响因子：
7.8
作者：
Owen, Jennifer L.;Sahay, Bikash;Mohamadzadeh, Mansour
通讯作者：
Mohamadzadeh, Mansour