Middle East Respiratory Syndrome Coronavirus Spike Protein Delivered by Modified Vaccinia Virus Ankara Efficiently Induces Virus-Neutralizing Antibodies

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8+T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.

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The Receptor Binding Domain of the New Middle East Respiratory Syndrome Coronavirus Maps to a 231-Residue Region in the Spike Protein That Efficiently Elicits Neutralizing Antibodies

Journal of Virology ◽

10.1128/jvi.01277-13 ◽

2013 ◽

Vol 87 (16) ◽

pp. 9379-9383 ◽

Cited By ~ 131

Author(s):

H. Mou ◽

V. S. Raj ◽

F. J. M. van Kuppeveld ◽

P. J. M. Rottier ◽

B. L. Haagmans ◽

...

Keyword(s):

Middle East ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Binding Domain ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

Receptor Binding Domain

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Genomic Sequencing and Analysis of Eight Camel-Derived Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Isolates in Saudi Arabia

Viruses ◽

10.3390/v12060611 ◽

2020 ◽

Vol 12 (6) ◽

pp. 611

Author(s):

Badr M. Al-Shomrani ◽

Manee M. Manee ◽

Sultan N. Alharbi ◽

Mussad A. Altammami ◽

Manal A. Alshehri ◽

...

Keyword(s):

Saudi Arabia ◽

Middle East ◽

Neutralizing Antibodies ◽

3D Structure ◽

Arabian Gulf ◽

Cell Epitope ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

Dromedary Camel ◽

Gulf Countries

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans; the second-largest and most deadly outbreak to date occurred in Saudi Arabia. The dromedary camel is considered a possible host of the virus and also to act as a reservoir, transmitting the virus to humans. Here, we studied evolutionary relationships for 31 complete genomes of betacoronaviruses, including eight newly sequenced MERS-CoV genomes isolated from dromedary camels in Saudi Arabia. Through bioinformatics tools, we also used available sequences and 3D structure of MERS-CoV spike glycoprotein to predict MERS-CoV epitopes and assess antibody binding affinity. Phylogenetic analysis showed the eight new sequences have close relationships with existing strains detected in camels and humans in Arabian Gulf countries. The 2019-nCov strain appears to have higher homology to both bat coronavirus and SARS-CoV than to MERS-CoV strains. The spike protein tree exhibited clustering of MERS-CoV sequences similar to the complete genome tree, except for one sequence from Qatar (KF961222). B cell epitope analysis determined that the MERS-CoV spike protein has 24 total discontinuous regions from which just six epitopes were selected with score values of >80%. Our results suggest that the virus circulates by way of camels crossing the borders of Arabian Gulf countries. This study contributes to finding more effective vaccines in order to provide long-term protection against MERS-CoV and identifying neutralizing antibodies.

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Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(20)30248-6 ◽

2020 ◽

Vol 20 (7) ◽

pp. 827-838 ◽

Cited By ~ 33

Author(s):

Till Koch ◽

Christine Dahlke ◽

Anahita Fathi ◽

Alexandra Kupke ◽

Verena Krähling ◽

...

Keyword(s):

Middle East ◽

Vaccinia Virus ◽

Vaccine Candidate ◽

Phase 1 ◽

Middle East Respiratory Syndrome ◽

Open Label ◽

Phase 1 Trial ◽

Vector Vaccine ◽

Modified Vaccinia Virus Ankara ◽

Open Label Phase

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Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA)

Infectious Diseases and Therapy ◽

10.1007/s40121-015-0091-9 ◽

2015 ◽

Vol 4 (4) ◽

pp. 491-501 ◽

Cited By ~ 86

Author(s):

Maren Eggers ◽

Markus Eickmann ◽

Juergen Zorn

Keyword(s):

Middle East ◽

Vaccinia Virus ◽

Povidone Iodine ◽

Middle East Respiratory Syndrome ◽

Virucidal Activity ◽

Modified Vaccinia Virus Ankara

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Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein

Virus Research ◽

10.1016/j.virusres.2014.10.007 ◽

2014 ◽

Vol 194 ◽

pp. 200-210 ◽

Cited By ~ 49

Author(s):

Shuai Xia ◽

Qi Liu ◽

Qian Wang ◽

Zhiwu Sun ◽

Shan Su ◽

...

Keyword(s):

Middle East ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

Entry Inhibitors

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Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.2.406-410.2004 ◽

2004 ◽

Vol 11 (2) ◽

pp. 406-410 ◽

Cited By ~ 18

Author(s):

Antonio Cosma ◽

Silja Bühler ◽

Rashmi Nagaraj ◽

Caroline Staib ◽

Anna-Lena Hammarin ◽

...

Keyword(s):

Immune Response ◽

Green Fluorescent Protein ◽

Vaccinia Virus ◽

High Throughput ◽

Neutralizing Antibodies ◽

Fluorescent Protein ◽

Safety Concern ◽

Neutralization Assay ◽

Modified Vaccinia Virus Ankara ◽

Green Fluorescent

ABSTRACT Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.

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Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach

Advances in Bioinformatics ◽

10.1155/2019/6815105 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Sabeena Mustafa ◽

Hanan Balkhy ◽

Musa Gabere

Keyword(s):

Middle East ◽

Antimicrobial Peptides ◽

Protein Interactions ◽

In Silico ◽

Therapeutic Option ◽

Binding Mode ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

In Silico Docking ◽

Peptide Database

There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.

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