title: Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines.
abstract: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Ma
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Chien-Te K
authors.initials: CT
authors.lastname: Tseng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA. Electronic address: ldu@nybloodcenter.org.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA; Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China. Electronic address: sjiang@nybloodcenter.org.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D017934:Coronavirus / Q000145:classification / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D014765:Viral Vaccines
keywords: MERS-CoV; Mucosal immune response; Neutralizing antibody; Receptor-binding domain; Spike protein; Systemic immune response