title: Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection.
abstract: Middle East respiratory syndrome (MERS) continues to raise worldwide concerns due to its pandemic potential. Increased MERS cases and no licensed MERS vaccines highlight the need to develop safe and effective vaccines against MERS. We have previously demonstrated that a receptor-binding domain (RBD) fragment containing residues 377-588 of MERS-coronavirus (MERS-CoV) spike protein is a critical neutralizing domain and an important vaccine target. Nevertheless, its optimal immunogen dosage and immunization interval, key factors for human-used vaccines that induce protective immunity, have never been investigated. In this study, we optimized these criteria using a recombinant MERS-CoV RBD protein fused with Fc (S377-588-Fc) and utilized the optimal immunization schedule to evaluate the protective efficacy of RBD against MERS-CoV infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice. Compared with one dose and 2 doses at 1-, 2-, and 3-week intervals, a regimen of 2 doses of this protein separated by an interval of 4 weeks induced the strongest antibody response and neutralizing antibodies against MERS-CoV infection, and maintained at a high level during the detection period. Notably, RBD protein at the optimal dosage and interval protected hDPP4-Tg mice against lethal MERS-CoV challenge, and the protection was positively correlated with serum neutralizing antibodies. Taken together, the optimal immunogen dosage and immunization interval identified in this study will provide useful guidelines for further development of MERS-CoV RBD-based vaccines for human use.
authors.affiliation: a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.|b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.|c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.|c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Wanbo
authors.initials: W
authors.lastname: Tai
authors.affiliation: b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: c 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: c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.affiliation: d Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Chien-Te K
authors.initials: CK
authors.lastname: Tseng
authors.affiliation: b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.|e Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Basic Medical College and Institute of Medical Microbiology , Fudan University , Shanghai , China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.|c 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: b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*; D000072417:Protein Domains / Q000276:immunology; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D064370:Spike Glycoprotein, Coronavirus; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: MERS-CoV; hDPP4-transgenic mice; neutralizing antibodies; optimal immunization interval; optimal immunogen dosage; protection; receptor-binding domain