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

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic stability and growth characteristics of MVA-MERS-S make it a suitable candidate vaccine for clinical testing. Vaccinated mice produced high levels of serum antibodies neutralizing MERS-CoV. Thus, MVA-MERS-S may serve for further development of an emergency vaccine against MERS-CoV.

[1]  S. Gilbert Clinical development of Modified Vaccinia virus Ankara vaccines. , 2013, Vaccine.

[2]  G. Sutter,et al.  Protective efficacy of Modified Vaccinia virus Ankara in preclinical studies. , 2013, Vaccine.

[3]  B. Bosch,et al.  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 , 2013, Journal of Virology.

[4]  L. Poon,et al.  The Emergence of Human Coronavirus EMC: How Scared Should We Be? , 2013, mBio.

[5]  K. To,et al.  Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation , 2013, The Journal of infectious diseases.

[6]  Christian Drosten,et al.  Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC , 2013, Nature.

[7]  Christian Drosten,et al.  The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies , 2013, Journal of Virology.

[8]  Alexander E. Gorbalenya,et al.  Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans , 2012, mBio.

[9]  A. Osterhaus,et al.  Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. , 2012, The New England journal of medicine.

[10]  R. Pebody,et al.  Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. , 2012, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[11]  G. Whittaker,et al.  Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein , 2012, Viruses.

[12]  T. Gallagher,et al.  Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence , 2012, Viruses.

[13]  J. Peiris,et al.  Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent FcγR Pathway , 2011, Journal of Virology.

[14]  Shibo Jiang,et al.  The spike protein of SARS-CoV — a target for vaccine and therapeutic development , 2009, Nature Reviews Microbiology.

[15]  P. Woo,et al.  Spike Protein, S, of Human Coronavirus HKU1: Role in Viral Life Cycle and Application in Antibody Detection , 2008, Experimental biology and medicine.

[16]  R. Baric,et al.  Animal models and vaccines for SARS-CoV infection , 2007, Virus Research.

[17]  R. Baric,et al.  Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease , 2007, Virus Research.

[18]  D. Ho,et al.  Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region , 2005, Journal of Virology.

[19]  L. Enjuanes,et al.  A Novel Sorting Signal for Intracellular Localization Is Present in the S Protein of a Porcine Coronavirus but Absent from Severe Acute Respiratory Syndrome-associated Coronavirus , 2004, Journal of Biological Chemistry.

[20]  B. Murphy,et al.  An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus , 2004, Nature Medicine.

[21]  B. Bosch,et al.  Cleavage Inhibition of the Murine Coronavirus Spike Protein by a Furin-Like Enzyme Affects Cell-Cell but Not Virus-Cell Fusion , 2004, Journal of Virology.

[22]  B. Moss,et al.  Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Moss,et al.  Development of a replication-deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. , 1996, Vaccine.

[24]  B. Moss,et al.  Nonreplicating vaccinia vector efficiently expresses recombinant genes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  G. Sutter,et al.  Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. , 1991, The Journal of general virology.

[26]  H. Vennema,et al.  Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization , 1990, Journal of virology.

[27]  R. Drillien,et al.  One hundred base pairs of 5' flanking sequence of a vaccinia virus late gene are sufficient to temporally regulate late transcription. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Kreijtz,et al.  Easy and efficient protocols for working with recombinant vaccinia virus MVA. , 2012, Methods in molecular biology.

[29]  J. Peiris,et al.  Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent Fc (cid:1) R Pathway (cid:1) , 2011 .

[30]  S. Shen,et al.  Expression, Glycosylation, and Modification of the Spike (S) Glycoprotein of SARS CoV , 2007, Methods in molecular biology.