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

• Published in: Vaccine Vol. 40; no. 5; pp. 714 - 725
• Main Authors: Yang, Ye Lin, Kim, Ju, Jeong, Yongsu, Jang, Yong-Suk
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 31.01.2022; Elsevier Limited
• Subjects: Adjuvant; Animal tissues; Animals; Antibiotics; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Body weight; Body weight loss; Cell-mediated immunity; Coronavirus Infections - prevention & control; Coronaviruses; Dipeptidyl-peptidase IV; Feces; Health risks; Immune system; Immunity; Immunization; Immunoglobulin G; Infections; Laboratory animals; Ligand; Ligands; Lymphocytes; Lymphocytes T; MERS-CoV; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus; Mucosal immunity; Peptidase; Peptidases; Peptides; Proteins; Public health; Recombinant antigen; Respiratory diseases; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Spleen; Transgenic mice; Vaccine; Vaccines; Viral Vaccines; Viruses; Weight loss; Middle East; United States > US; Germany; Ab; hDPP4; M cell; Ligand; E; Ag; Recombinant antigen; MERS-CoV; upE; hDPP4-Tg; M; N; DPP4; SC; FITC; IFN-γ; SE; S; RBD; FBS; Adjuvant; Th1; PFU; Th2; MERS-CoV-S; PBS; IL; qRT-PCR; Vaccine; ELISPOT; APC; TNF-α; PE; CTL; MERS; S-RBD; Ig; PCR; ELISA
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.12.057

•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. 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.