A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: Implication for developing therapeutics and vaccines

Lanying Du, Zhihua Kou, Cuiqing Ma, Xinrong Tao, Lili Wang, Guangyu Zhao, Yaoqing Chen, Fei Yu, Chien-Te Tseng, Yusen Zhou, Shibo Jiang

Research output: Contribution to journalArticle

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Abstract

An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERSCoV infection.

Original languageEnglish (US)
Article numbere81587
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 4 2013

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Coronavirus Infections
Dipeptidyl Peptidase 4
Middle East
Neutralizing Antibodies
neutralizing antibodies
Antibody Formation
Vaccines
vaccines
Immunoglobulin Fc Fragments
Pulmonary diseases
therapeutics
receptors
Protein S
Infection
Recombinant Proteins
infection
Proteins
proteins
Immunoglobulin G
Amino Acids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses : Implication for developing therapeutics and vaccines. / Du, Lanying; Kou, Zhihua; Ma, Cuiqing; Tao, Xinrong; Wang, Lili; Zhao, Guangyu; Chen, Yaoqing; Yu, Fei; Tseng, Chien-Te; Zhou, Yusen; Jiang, Shibo.

In: PLoS One, Vol. 8, No. 12, e81587, 04.12.2013.

Research output: Contribution to journalArticle

Du, Lanying ; Kou, Zhihua ; Ma, Cuiqing ; Tao, Xinrong ; Wang, Lili ; Zhao, Guangyu ; Chen, Yaoqing ; Yu, Fei ; Tseng, Chien-Te ; Zhou, Yusen ; Jiang, Shibo. / A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses : Implication for developing therapeutics and vaccines. In: PLoS One. 2013 ; Vol. 8, No. 12.
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