The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

中文翻译：

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应用抗菌肽 LL-37 作为中东呼吸综合征冠状病毒抗原的佐剂，在鼻内免疫后诱导针对病毒感染的有效保护性免疫反应。

人类抗菌肽 LL-37 在包括树突细胞在内的各种免疫细胞中具有趋化和调节活性。由于其特性，LL-37可以被认为是疫苗开发的佐剂。在这项研究中，我们通过在 C57BL/6 和人二肽基肽酶 4 (hDPP4)-转基因中进行鼻内免疫，证实了 LL-37 在针对中东呼吸综合征冠状病毒 (MERS-CoV) 的粘膜疫苗开发中可能的佐剂活性 ( hDPP4-Tg) 小鼠。使用 MERS-CoV 刺突蛋白 (S-RBD) 的受体结合域 (RBD) 与 LL-37 (S-RBD-LL-37) 重组的鼻内免疫诱导了具有病毒中和活​​性的有效粘膜 IgA 和全身 IgG 反应，与 S-RBD 相比。与 S-RBD 相比，用 S-RBD-LL-37 鼻内免疫的小鼠肺部也能有效诱导 Ag 特异性 CTL 刺激。重要的是，用 S-RBD-LL-37 对 hDPP4-Tg 小鼠进行鼻内免疫导致感染 MERS-CoV 后免疫细胞浸润到肺部的情况减少。最后，用 S-RBD-LL-37 对 hDPP4-Tg 小鼠进行鼻内免疫可增强保护功效，增加存活率并减少感染 MERS-CoV 后的体重减轻。总的来说，这些结果表明 S-RBD-LL-37 是一种有效的抗 MERS-CoV 感染的鼻内疫苗候选分子。用 S-RBD-LL-37 对 hDPP4-Tg 小鼠进行鼻内免疫可增强保护功效，并在感染 MERS-CoV 后增加存活率并减少体重减轻。总的来说，这些结果表明 S-RBD-LL-37 是一种有效的抗 MERS-CoV 感染的鼻内疫苗候选分子。用 S-RBD-LL-37 对 hDPP4-Tg 小鼠进行鼻内免疫可增强保护功效，并在感染 MERS-CoV 后增加存活率并减少体重减轻。总的来说，这些结果表明 S-RBD-LL-37 是一种有效的抗 MERS-CoV 感染的鼻内疫苗候选分子。