A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection

Wanbo Tai, Guangyu Zhao, Shihun Sun, Yan Guo, Yufei Wang, Xinrong Tao, Chien-Te Tseng, Fang Li, Shibo Jiang, Lanying, Du, Yusen Zhou

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)375-382
Number of pages8
JournalVirology
Volume499
DOIs
StatePublished - Dec 1 2016

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Coronavirus Infections
Dipeptidyl Peptidase 4
Transgenic Mice
Infection
Vaccines
Neutralizing Antibodies
Protein Binding

Keywords

  • Foldon trimerization motif
  • hDPP4-transgenic mice
  • MERS
  • MERS-CoV
  • Neutralization
  • Protection
  • Receptor-binding domain
  • Spike protein

ASJC Scopus subject areas

  • Virology

Cite this

A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. / Tai, Wanbo; Zhao, Guangyu; Sun, Shihun; Guo, Yan; Wang, Yufei; Tao, Xinrong; Tseng, Chien-Te; Li, Fang; Jiang, Shibo; Du, Lanying,; Zhou, Yusen.

In: Virology, Vol. 499, 01.12.2016, p. 375-382.

Research output: Contribution to journalArticle

Tai, Wanbo ; Zhao, Guangyu ; Sun, Shihun ; Guo, Yan ; Wang, Yufei ; Tao, Xinrong ; Tseng, Chien-Te ; Li, Fang ; Jiang, Shibo ; Du, Lanying, ; Zhou, Yusen. / A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. In: Virology. 2016 ; Vol. 499. pp. 375-382.
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