A novel human coronavirus, hCoV-EMC, was recently identified in the Middle East. It was reported to cause severe acute respiratory syndrome (SARS)-like disease, having killed 5 persons and sickened 4 others since June of 2012. Because hCoV-EMC is genetically related to SARS-CoV, the causative agent of the deadly SARS that killed 774 people among 8,098 infected cases during the 2003 outbreak, it has raised great concerns about the potential pandemic spread of this lethal disease. Therefore, developing vaccines to prevent the potential outbreak of hCoV-EMC infection is urgently needed. We have previously shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein S1 subunit contains critical neutralizing domain (CND) and that the subunit vaccine based on the RBD/CND can induce potent neutralizing antibody responses and protection against SARS-CoV infection in animal models. By comparing and analyzing the S protein sequences of SARS-CoV and hCoV- EMC, we found that hCoV-EMC S protein S1 subunit also contains a region that exhibited a core structure very similar to that of RBD in SARS-CoV S protein. We also found that a recombinant protein containing the truncated ectodomain of hCoV-EMC S protein fused to Fc induced S-specific antibodies with neutralizing activity, suggesting that hCoV-EMC S protein does contain CND(s). We therefore hypothesize that CND(s) can be identified from the hCoV-EMC S protein, based which an effective vaccine with ability to elicit strong neutralizing antibody responses and protective immunity against hCoV-EMC infection can be developed.
The specific aims of this proposal are to: 1) identify CND(s) from hCoV- EMC S protein and its subunits, 2) design CND-based subunit hCoV-EMC vaccines, 3) optimize immunization regimens for vaccination of animals with a selected hCoV-EMC vaccine candidate, and 4) evaluate the in vivo protective immunity of the selected hCoV-EMC vaccine candidate against viral challenge in an animal model. The long-term goal of the proposed study is to develop an effective and safe CND-based subunit vaccine against the newly identified SARS-like virus hCoV-EMC that may cause a future outbreak in humans.

Public Health Relevance

A novel human coronavirus, hCoV-EMC, which causes severe acute respiratory syndrome (SARS)-like disease, was identified recently, raising concerns about the potential pandemic spread of this lethal disease. Accordingly, development of vaccines to prevent the outbreak of this emerging disease is urgently needed. Our objective is to identify a critical neutralizing domain (CND) from hCoV-EMC spike protein and to develop an effective and safe CND-based subunit vaccine for preventing hCoV-EMC infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI109094-01
Application #
8619937
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Stemmy, Erik J
Project Start
2013-12-15
Project End
2015-11-30
Budget Start
2013-12-15
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$190,950
Indirect Cost
$78,450
Name
New York Blood Center
Department
Type
DUNS #
073271827
City
New York
State
NY
Country
United States
Zip Code
10065
Du, Lanying; Yang, Yang; Zhou, Yusen et al. (2017) MERS-CoV spike protein: a key target for antivirals. Expert Opin Ther Targets 21:131-143
Wang, Yufei; Tai, Wanbo; Yang, Jie et al. (2017) Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection. Hum Vaccin Immunother 13:1615-1624
Tai, Wanbo; Wang, Yufei; Fett, Craig A et al. (2017) Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants. J Virol 91:
Tai, Wanbo; Zhao, Guangyu; Sun, Shihun et al. (2016) A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. Virology 499:375-382
Du, Lanying; Tai, Wanbo; Zhou, Yusen et al. (2016) Vaccines for the prevention against the threat of MERS-CoV. Expert Rev Vaccines 15:1123-34
Qiu, Hongjie; Sun, Shihui; Xiao, He et al. (2016) Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. Antiviral Res 132:141-8
Zhang, Naru; Channappanavar, Rudragouda; Ma, Cuiqing et al. (2016) Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cell Mol Immunol 13:180-90
Du, Lanying; Tai, Wanbo; Yang, Yang et al. (2016) Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. Nat Commun 7:13473
Zhang, Naru; Tang, Jian; Lu, Lu et al. (2015) Receptor-binding domain-based subunit vaccines against MERS-CoV. Virus Res 202:151-9
Du, Lanying; Jiang, Shibo (2015) Middle East respiratory syndrome: current status and future prospects for vaccine development. Expert Opin Biol Ther 15:1647-51

Showing the most recent 10 out of 16 publications