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Title: Evaluation of candidate vaccine approaches for MERS-CoV

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms8712· OSTI ID:1214709

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357; W-31-109-ENG-38
OSTI ID:
1214709
Journal Information:
Nature Communications, Vol. 6; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 190 works
Citation information provided by
Web of Science

References (64)

Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. journal October 1996
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus journal September 2013
A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial journal November 2008
Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice journal May 2014
Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody journal April 2013
Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines journal April 2014
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 June 2013
Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses journal January 2005
Refinement of severely incomplete structures with maximum likelihood in BUSTER–TNT journal November 2004
Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26 journal July 2013
Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility journal January 2014
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 journal December 2013
A decade after SARS: strategies for controlling emerging coronaviruses text January 2013
DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials journal December 2011
Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013 journal June 2014
Rapid generation of a mouse model for Middle East respiratory syndrome journal March 2014
Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus journal October 2013
Effects of Human Anti-Spike Protein Receptor Binding Domain Antibodies on Severe Acute Respiratory Syndrome Coronavirus Neutralization Escape and Fitness text January 2014
Phase I clinical evaluation of a six-plasmid multiclade HIV-1 DNA candidate vaccine journal May 2007
DNA Priming Prior to Inactivated Influenza A(H5N1) Vaccination Expands the Antibody Epitope Repertoire and Increases Affinity Maturation in a Boost-Interval–Dependent Manner in Adults journal April 2013
Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain journal May 2009
Rapid generation of a mouse model for Middle East respiratory syndrome text January 2014
Effects of Human Anti-Spike Protein Receptor Binding Domain Antibodies on Severe Acute Respiratory Syndrome Coronavirus Neutralization Escape and Fitness journal September 2014
MolProbity : all-atom structure validation for macromolecular crystallography journal December 2009
Inhibition of Middle East Respiratory Syndrome Coronavirus Infection by Anti-CD26 Monoclonal Antibody journal September 2013
Sustained Peptide-Specific Gamma Interferon T-Cell Response in Rhesus Macaques Immunized with Human Immunodeficiency Virus gag DNA Vaccines journal October 2002
Modulation of immune responses in mice to recombinant antigens from PE and PPE families of proteins of Mycobacterium tuberculosis by the Ribi adjuvant journal October 2007
A decade after SARS: strategies for controlling emerging coronaviruses journal November 2013
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Does Not Replicate in Syrian Hamsters journal July 2013
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
DNA-Mediated Immunization in Mice Induces a Potent MHC Class I-Restricted Cytotoxic T Lymphocyte Response to the Hepatitis B Envelope Protein journal November 1995
Three-dimensional structure of an Fv from a human IgM immunoglobulin journal November 1992
A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice journal April 2004
Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia journal April 2014
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution text January 2014
Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies journal July 2007
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
A Generic Approach to Pathological Lung Segmentation journal December 2014
Two is better than one journal December 2011
Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein journal April 2014
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen journal August 2020
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution journal April 2014
Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells journal July 1988
Assessing the pandemic potential of MERS-CoV journal August 2013
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome journal December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation journal February 2021
Rapid lateral flow immunoassay for the fluorescence detection of SARS-CoV-2 RNA journal December 2020
Coronavirus IBV: Structural Characterization of the Spike Protein journal December 1983
Features and development of Coot journal March 2010
A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein journal April 2014
Is MERS another SARS? journal September 2013
Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study journal September 2013
Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk journal August 2013
Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity journal June 2004
Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine Priming Effect journal April 2013
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus text January 2013
A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates journal June 2005
Modulation of the Immune Response to the Severe Acute Respiratory Syndrome Spike Glycoprotein by Gene-Based and Inactivated Virus Immunization journal October 2005
Structure of Severe Acute Respiratory Syndrome Coronavirus Receptor-binding Domain Complexed with Neutralizing Antibody journal April 2006
Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo journal May 2021
A Simple Method of Estimating Fifty per cent Endpoints12 journal May 1938
Phaser crystallographic software journal July 2007
DNA vaccination: antigen presentation and the induction of immunity journal December 2000

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Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein journal March 2020
A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation journal July 2016
A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein journal January 2017
Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies journal November 2019
Antibody-mediated protection against MERS-CoV in the murine model journal July 2019
Prospects for a MERS-CoV spike vaccine journal August 2018
Development of Middle East Respiratory Syndrome Coronavirus vaccines – advances and challenges journal November 2017
Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice journal July 2019
SARS and MERS: recent insights into emerging coronaviruses journal June 2016
Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches journal April 2017
Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain journal January 2019
Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein journal January 2019
MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques journal March 2016
MERS-CoV spike protein: Targets for vaccines and therapeutics journal September 2016
From SARS to MERS, Thrusting Coronaviruses into the Spotlight journal January 2019
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 journal October 2016
Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD journal September 2019
Toward Developing a Preventive MERS-CoV Vaccine—Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14–15, 2015 journal August 2016
Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein journal July 2018
Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas journal March 2019
Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus journal July 2019
Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections journal March 2019
Rapid development of a DNA vaccine for Zika virus journal September 2016
Middle East respiratory syndrome coronavirus: a comprehensive review journal January 2016
Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus journal July 2016
Coronaviruses — drug discovery and therapeutic options journal February 2016
Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases journal December 2015
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein journal July 2019
Molecular aspects of MERS-CoV journal May 2017
Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism journal January 2019
Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus journal August 2019
Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus journal August 2017
Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar journal February 2019
Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody journal September 2015
Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein journal March 2017
MERS-CoV spike protein: a key target for antivirals journal December 2016
Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study journal November 2019
ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice journal June 2017
DNA vaccine encoding Middle East respiratory syndrome coronavirus S1 protein induces protective immune responses in mice journal April 2017
Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model journal August 2018
CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice journal December 2018
A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model journal July 2019
Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus journal October 2017
Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus journal June 2018
Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development journal October 2017
Production of a Monoclonal Antibody Targeting the M Protein of MERS-CoV for Detection of MERS-CoV Using a Synthetic Peptide Epitope Formulated with a CpG–DNA–Liposome Complex journal July 2018
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen journal August 2017
Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses journal February 2020
Middle East respiratory syndrome: current status and future prospects for vaccine development journal July 2015
Antibodies and vaccines against Middle East respiratory syndrome coronavirus journal January 2019
Vaccines for the prevention against the threat of MERS-CoV journal April 2016
Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus journal April 2018
Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains journal April 2017
Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient journal May 2018
A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization journal February 2018
A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry journal March 2019
Narrative review of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: updates and implications for practice journal July 2019
Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach journal November 2018
Viromimetic STING Agonist‐Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus journal April 2019

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