Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious disease that affects cloven-hoofed animals and can lead to serious economic losses and social effects. Therefore, a safe and effective subunit vaccine is required to prevent and control FMD. Dendritic cells (DCs) are a type of professional antigen presenting cell (APC). Immature DCs are typically stimulated by various adjuvants via immune receptors (e.g., toll-like receptor 4 [TLR4]), which activate DCs to induce their maturation. TLR4 has been well-established to induce both innate and adaptive immune responses to various external microbial or internal damage-related molecular patterns. In this study, the multi-epitope immunogen, HAO, of foot-and-mouth disease virus (FMDV) serotypes A and O was fused with the recombinant protein, heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist, to obtain a new recombinant fusion protein, termed HAO-HBHA. HAO-HBHA was found to be highly efficient at activating murine DCs by the TLR4 pathway, both in vitro and in vivo. HAO-HBHA elicited strong specific humoral immune responses detected with an ELISA and virus neutralizing antibody test (VNT). HAO-HBHA also elevated the cellular immune responses, as indicated by intracellular cytokine (e.g., IFN-γ, TNF-α, IL-4, IL-6, IL-10, and IL-12p70) expression in Th1 and Th2 cells. As a TLR4 agonist, HBHA has significant advantages for enhancing the immune efficacy of a FMDV serotype A and O bivalent multi-epitope vaccine. These findings provide a novel strategy for the development of a safe and effective multi-epitope vaccine candidate against FMDV and further extends the application of TLR agonist-based vaccine platforms.

中文翻译：

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通过将多个表位与结核分枝杆菌肝素结合血凝素（HBHA）（一种新型的TLR4激动剂）融合，增强了针对A型和O型口蹄疫病毒的多表位疫苗的功效。

口蹄疫（FMD）是一种急性，严重和高度传染性疾病，影响到偶蹄类动物，并可能导致严重的经济损失和社会影响。因此，需要一种安全有效的亚单位疫苗来预防和控制口蹄疫。树突状细胞（DC）是一种专业抗原呈递细胞（APC）。不成熟的DC通常通过免疫佐剂（例如Toll样受体4 [TLR4]）被各种佐剂刺激，这些受体激活DC以诱导其成熟。TLR4已被公认可以诱导对各种外部微生物或内部损伤相关分子模式的先天和适应性免疫应答。在这项研究中，将口蹄疫病毒（FMDV）血清型A和O的多表位免疫原（HAO）与重组蛋白肝素结合血凝素（HBHA）融合在一起，一种新的TLR4激动剂，以获得称为HAO-HBHA的新重组融合蛋白。发现HAO-HBHA通过TLR4途径在体外和体内均可有效激活鼠DC。HAO-HBHA引发了通过ELISA和病毒中和抗体测试（VNT）检测到的强特异性体液免疫反应。正如在Th1和Th2细胞中的细胞内细胞因子（例如IFN-γ，TNF-α，IL-4，IL-6，IL-10和IL-12p70）表达所表明的那样，HAO-HBHA还提高了细胞免疫应答。作为TLR4激动剂，HBHA在增强FMDV血清型A和O二价多表位疫苗的免疫效力方面具有显着优势。这些发现为开发针对FMDV的安全有效的多表位候选疫苗提供了新的策略，并进一步扩展了基于TLR激动剂的疫苗平台的应用。