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. Issue 5 (31st January 2022)

• Record Type: Journal Article
• Authors: Yang, Ye Lin; Kim, Ju; Jeong, Yongsu; Jang, Yong-Suk
• Is Part Of: Vaccine. Volume 40:Issue 5(2022)
• Page Start: 714
• Page End: 725
• Publication Date: 2022-01-31
• Subjects: Adjuvant -- Ligand -- MERS-CoV -- Recombinant antigen -- Vaccine; Ab antibody -- Ag antigen -- APC allophycocyanin -- CTL cytotoxic T lymphocyte -- DPP4 dipeptidyl peptidase 4 -- E envelope -- ELISA enzyme-linked immunosorbent assay -- ELISPOT enzyme-linked immunosorbent spot -- FBS fetal bovine serum -- FITC fluorescein isothiocyanate -- hDPP4 human DPP4 -- hDPP4-Tg hDPP4-transgenic -- IFN-γ interferon-γ -- Ig immunoglobulin -- IL interleukin -- M membrane -- M cell microfold cell -- MERS Middle East respiratory syndrome -- MERS-CoV MERS-coronavirus -- MERS-CoV-S MERS-CoV spike -- N nucleocapsid -- PBS phosphate-buffered saline -- PCR polymerase chain reaction -- PE phycoerythrin -- PFU plaque-forming unit -- qRT-PCR quantitative real-time reverse-transcription PCR -- RBD receptor-binding domain -- S spike -- SC secreting cell -- SE standard error -- S-RBD RBD of the S1 subunit -- Th1 T helper 1 -- Th2 T helper 2 -- TNF-α tumor necrosis factor-α -- upE upstream E; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.12.057
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A vaccine against MERS-CoV, which infects via the respiratory route, is needed. We previously identified a Co4B ligand which can enhance Ag delivery to nasal mucosa. We prepared Co4B-conjugated receptor binding domain of MERS-CoV spike protein. We intranasally immunized C57BL/6 and hDPP4-Tg mice with S-RBD-Co4B. Intranasal immunization of S-RBD-Co4B induced efficient Ag-specific immune response. Abstract: 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 Ag-specific 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 Co4B-conjugated 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.