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Published on: April 15, 2014
Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic
Yufei Wang1,2,3, Wanbo Tai2,3, Jie Yang2
1a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.
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.
Insights
Optimizing the Middle East respiratory syndrome (MERS) vaccine involved determining the best immunogen dosage and immunization schedule. A two-dose regimen, spaced four weeks apart, yielded the strongest protective immune response in mice against MERS-CoV.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Middle East respiratory syndrome (MERS) poses a significant global health threat due to its pandemic potential.
- The lack of licensed MERS vaccines necessitates the development of safe and effective vaccine candidates.
- The MERS-coronavirus (MERS-CoV) spike protein's receptor-binding domain (RBD) is a validated target for neutralizing antibodies.
Purpose of the Study:
- To optimize the immunogen dosage and immunization interval for a MERS-CoV RBD-based vaccine.
- To evaluate the protective efficacy of the optimized MERS-CoV RBD vaccine in a preclinical mouse model.
Main Methods:
- A recombinant MERS-CoV RBD protein fused with Fc (S377-588-Fc) was used as the immunogen.
- Different dosages and immunization intervals (1, 2, or 3 weeks) were tested in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice.
- The optimal immunization schedule was used to assess protection against lethal MERS-CoV challenge.
Main Results:
- A regimen of two doses of the RBD protein separated by a 4-week interval induced the strongest and most sustained antibody and neutralizing antibody responses.
- This optimized immunization strategy provided significant protection against lethal MERS-CoV challenge in hDPP4-Tg mice.
- Protection levels correlated positively with serum neutralizing antibody titers.
Conclusions:
- The identified optimal immunogen dosage and immunization interval provide crucial guidelines for developing MERS-CoV RBD-based vaccines.
- Further development of MERS vaccines can leverage these findings to enhance protective immunity in humans.
- This study contributes to preparedness against MERS outbreaks through optimized vaccine strategies.
