Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
Bibliographical noteFunding Information:
This study was supported by China National Program of Infectious Disease Fund ( 2014ZX10004001004 ) to YZ, and NIH Grants ( R01AI098775 , U01AI124260 , and R21AI109094 ) to LD and SJ. We thank Drs. Dimiter S. Dimitrov and Tianlei Ying at the National Institutes of Health for providing m336, m337 and m338 mAbs.
- Foldon trimerization motif
- Receptor-binding domain
- Spike protein
- hDPP4-transgenic mice