State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, 225009, China.
State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China.
Mol Immunol. 2020 May;121:118-126. doi: 10.1016/j.molimm.2020.02.018. Epub 2020 Mar 18.
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.
口蹄疫（FMD）是一种急性、严重且高度传染性的疾病，影响偶蹄动物，可导致严重的经济损失和社会影响。因此，需要安全有效的亚单位疫苗来预防和控制 FMD。树突状细胞（DCs）是一种专业的抗原提呈细胞（APC）。未成熟的 DCs 通常通过各种免疫受体（例如，Toll 样受体 4 [TLR4]）被各种佐剂刺激，这会激活 DCs 诱导其成熟。TLR4 已被证实可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反应。在这项研究中，口蹄疫病毒（FMDV）血清型 A 和 O 的多表位免疫原 HAO 与新型 TLR4 激动剂肝素结合血凝素（HBHA）融合，得到一种新的重组融合蛋白，称为 HAO-HBHA。HAO-HBHA 通过 TLR4 途径在体外和体内均能高效激活小鼠 DCs。HAO-HBHA 引起了强烈的特异性体液免疫反应，ELISA 和病毒中和抗体试验（VNT）均能检测到。HAO-HBHA 还提高了细胞免疫反应，Th1 和 Th2 细胞中细胞因子（例如 IFN-γ、TNF-α、IL-4、IL-6、IL-10 和 IL-12p70）的表达表明了这一点。作为 TLR4 激动剂，HBHA 对增强 FMDV 血清型 A 和 O 二价多表位疫苗的免疫效果具有重要优势。这些发现为开发安全有效的 FMDV 多表位疫苗候选物提供了新策略，并进一步扩展了 TLR 激动剂疫苗平台的应用。
