Bovine viral diarrhea virus (BVDV) is one of the main causes of infectious diseases in cattle and causes large financial losses to the cattle industry worldwide. In this study, Lactobacillus casei strain W56 (Lc W56) was used as antigen deliver carrier to construct a recombinant Lactobacillus vaccine pPG-E2-ctxB/Lc W56 constitutively expressing BVDV E2 protein fused with cholera toxin B subunit (ctxB) as an adjuvant, and its immunogenicity against BVDV infection in mice model by oral route was explored. Our results suggested that pPG-E2-ctxB/Lc W56 can effectively activate dendritic cells (DCs) in the Peyer’s patches, up-regulate the expression of Bcl-6, and promote T-follicular helper (Tfh) cells differentiation, as well as enhance B lymphocyte proliferation and promote them differentiate into specific IgA-secreting plasma cells, secreting anti-E2 mucosal sIgA antibody with BVDV-neutralizing activity. Moreover, significant levels (p < 0.01) of BVDV-neutralizing antigen-specific serum antibodies were induced in the pPG-E2-ctxB/LC W56 group post-vaccination. The recombinant Lactobacillus vaccine can induce cellular immune responses, and significant levels (p < 0.01) of Th1-associated cytokines (IL-2, IL-12, and IFN-γ), Th2-associated cytokines (IL-4, IL-10) and Th17-associated cytokine (IL-17) were determined in the serum of vaccinated mice. Significantly, the recombinant Lactobacillus vaccine provides immune protection against BVDV infection, which can be cleared effectively by the vaccine post-challenge in orally vaccinated animals. The genetically engineered Lactobacillus vaccine constructed in this study is immunogenic in mice and can induce mucosal, humoral, and cellular immune responses, providing effective anti-BVDV immune protection. It thus represents a promising strategy for vaccine development against BVDV.

中文翻译：

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表达牛病毒性腹泻病毒E2蛋白的重组干酪乳杆菌W56联合霍乱毒素B亚基作为佐剂的免疫原性评价


牛病毒性腹泻病毒（BVDV）是牛传染性疾病的主要原因之一，给全世界养牛业造成巨大的经济损失。本研究以干酪乳杆菌菌株W56（Lc W56）为抗原递送载体，构建了重组乳杆菌疫苗pPG-E2-ctxB/Lc W56，其组成型表达与霍乱毒素B亚基（ctxB）融合的BVDV E2蛋白作为佐剂，并探讨了其口服途径对小鼠模型BVDV感染的免疫原性。我们的结果表明，pPG-E2-ctxB/Lc W56 可以有效激活派尔氏淋巴结中的树突状细胞 (DC)，上调 Bcl-6 的表达，促进滤泡辅助 T (Tfh) 细胞分化，以及增强B淋巴细胞增殖并促进其分化为特异性IgA分泌浆细胞，分泌具有BVDV中和活性的抗E2粘膜sIgA抗体。此外，在疫苗接种后，pPG-E2-ctxB/LC W56 组中诱导了显着水平的 BVDV 中和抗原特异性血清抗体（p < 0.01）。重组乳杆菌疫苗可诱导细胞免疫反应，并显着水平 (p < 0.01) Th1 相关细胞因子（IL-2、IL-12 和 IFN-γ）、Th2 相关细胞因子（IL-4、IL- 10) 和 Th17 相关细胞因子 (IL-17) 在接种疫苗的小鼠血清中进行测定。值得注意的是，重组乳杆菌疫苗提供了针对 BVDV 感染的免疫保护，在口服疫苗接种的动物中，疫苗攻击后可以有效清除这种感染。本研究构建的基因工程乳杆菌疫苗在小鼠体内具有免疫原性，可诱导粘膜、体液和细胞免疫反应，提供有效的抗 BVDV 免疫保护。 因此，它代表了一种有前景的 BVDV 疫苗开发策略。