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Application of Antimicrobial Peptide LL-37 as an Adjuvant for Middle East Respiratory Syndrome-Coronavirus Antigen Induces an Efficient Protective Immune Response Against Viral Infection After Intranasal Immunization

  • Ju Kim (Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University) ;
  • Ye Lin Yang (Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University) ;
  • Yongsu Jeong (Graduate School of Biotechnology, Kyung Hee University) ;
  • Yong-Suk Jang (Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University)
  • 투고 : 2022.04.09
  • 심사 : 2022.08.22
  • 발행 : 2022.10.31

초록

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.

키워드

과제정보

This work was supported by grants from the Basic Science Research Program (2019R1A2C2004711) through the National Research Foundation, which is funded by the Korean Ministry of Science and ICT, and the Basic Science Research Program through the NRF, which is funded by the Ministry of Education (2017R1A6A1A03015876). Y. L. Yang was supported by the BK21 FOUR program in the Department of Bioactive Material Sciences. Some experiments were performed using instruments installed in the Center for University-Wide Research Facilities (CURF) at Jeonbuk National University.

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