Intranasal immunization with a Middle East respiratory syndrome-coronavirus antigen conjugated to the M-cell targeting ligand Co4B enhances antigen-specific mucosal and systemic immunity and protects against infection

被引:2
作者
Yang, Ye Lin [1 ,2 ]
Kim, Ju [3 ,4 ]
Jeong, Yongsu [5 ]
Jang, Yong-Suk [1 ,2 ,3 ,4 ]
机构
[1] Jeonbuk Natl Univ, Dept Bioact Mat Sci, Jeonju 54896, South Korea
[2] Jeonbuk Natl Univ, Res Ctr Bioact Mat, Jeonju 54896, South Korea
[3] Jeonbuk Natl Univ, Dept Mol Biol, Jeonju 54896, South Korea
[4] Jeonbuk Natl Univ, Inst Mol Biol & Genet, Jeonju 54896, South Korea
[5] Kyung Hee Univ, Grad Sch Biotechnol, Yongin 17104, South Korea
基金
新加坡国家研究基金会;
关键词
Adjuvant; Ligand; MERS-CoV; Recombinant antigen; Vaccine; RECEPTOR-BINDING DOMAIN; MERS-COV; SUBUNIT VACCINE; SPIKE PROTEIN; RESPONSES; PATHOGENESIS; ACTIVATION; ANTIBODIES; INFLUENZA; VIRUS;
D O I
10.1016/j.vaccine.2021.12.057
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Middle East respiratory syndrome (MERS) is a threat to public health worldwide. A vaccine against the causative agent of MERS, MERS-coronavirus (MERS-CoV), is urgently needed. We previously identified a peptide ligand, Co4B, which can enhance antigen (Ag) delivery to the nasal mucosa and promote Agspecific mucosal and systemic immune responses following intranasal immunization. MERS-CoV infects via the respiratory route; thus, we conjugated the Co4B ligand to the MERS-CoV spike protein receptor binding domain (S-RBD), and used this to intranasally immunize C57BL/6 and human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice. Ag-specific mucosal immunoglobulin (Ig) A and systemic IgG, together with virus-neutralizing activities, were highly induced in mice immunized with Co4Bconjugated S-RBD (S-RBD-Co4B) compared to those immunized with unconjugated S-RBD. Ag-specific T cell-mediated immunity was also induced in the spleen and lungs of mice intranasally immunized with S-RBD-Co4B. Intranasal immunization of hDPP4-Tg mice with S-RBD-Co4B reduced immune cell infiltration into the tissues of virus-challenged mice. Finally, S-RBD-Co4B-immunized mice exhibited were better protected against infection, more likely to survive, and exhibited less body weight loss. Collectively, our results suggest that S-RBD-Co4B could be used as an intranasal vaccine candidate against MERS-CoV infection. CO 2021 Elsevier Ltd. All rights reserved.
引用
收藏
页码:714 / 725
页数:12
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