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Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection
- Source :
- Human Vaccines & Immunotherapeutics
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
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.
- Subjects :
- Male
0301 basic medicine
Genetically modified mouse
Protective immunity
Immunogen
Transgene
Immunology
Mice, Transgenic
Mice, SCID
Biology
law.invention
03 medical and health sciences
Protein Domains
law
Animals
Humans
Immunology and Allergy
Immunization Schedule
Dipeptidyl peptidase-4
Pharmacology
Mice, Inbred BALB C
Vaccines, Synthetic
Spike Protein
Viral Vaccines
Research Papers
Virology
030104 developmental biology
Immunization
Spike Glycoprotein, Coronavirus
Middle East Respiratory Syndrome Coronavirus
Recombinant DNA
Female
Coronavirus Infections
Subjects
Details
- ISSN :
- 2164554X and 21645515
- Volume :
- 13
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Human Vaccines & Immunotherapeutics
- Accession number :
- edsair.doi.dedup.....1c7e715b38d392ba64b03b25ffcda80d
- Full Text :
- https://doi.org/10.1080/21645515.2017.1296994