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Open AccessArticle

Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice

1
Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Korea
2
Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Korea
3
Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Korea
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(4), 635; https://doi.org/10.3390/vaccines8040635
Received: 23 September 2020 / Revised: 24 October 2020 / Accepted: 30 October 2020 / Published: 1 November 2020
(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the dose and administration route need optimization to achieve optimal protection. We here investigated the potential use of human β-defensin 2 (HBD 2) as an adjuvant to enhance the protection provided by MERS-CoV vaccination. We found that immunization of human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice with spike protein receptor-binding domain (S RBD) conjugated with HBD 2 (S RBD-HBD 2) induced potent antigen (Ag)-specific adaptive immune responses and protected against MERS-CoV infection. In addition, immunization with S RBD-HBD 2 alleviated progressive pulmonary fibrosis in the lungs of MERS-CoV-infected hDPP4-Tg mice and suppressed endoplasmic reticulum stress signaling activation upon viral infection. Compared to intramuscular administration, intranasal administration of S RBD-HBD 2 induced more potent mucosal IgA responses and was more effective for protecting against intranasal MERS-CoV infection. In conclusion, our findings suggest that HBD 2 potentiates Ag-specific immune responses against viral Ag and can be used as an adjuvant enhancing the immunogenicity of subunit vaccine candidates against MERS-CoV. View Full-Text
Keywords: adjuvant; antibody; defensin; MERS-CoV; vaccine adjuvant; antibody; defensin; MERS-CoV; vaccine
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MDPI and ACS Style

Kim, J.; Yang, Y.L.; Jeong, Y.; Jang, Y.-S. Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice. Vaccines 2020, 8, 635. https://doi.org/10.3390/vaccines8040635

AMA Style

Kim J, Yang YL, Jeong Y, Jang Y-S. Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice. Vaccines. 2020; 8(4):635. https://doi.org/10.3390/vaccines8040635

Chicago/Turabian Style

Kim, Ju; Yang, Ye L.; Jeong, Yongsu; Jang, Yong-Suk. 2020. "Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice" Vaccines 8, no. 4: 635. https://doi.org/10.3390/vaccines8040635

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