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J Infect Dis. Platform Strategies for Rapid Response Against Emerging Coronaviruses: MERS-CoV Serologic and Antigenic Relationships in Vaccine Design
[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Platform Strategies for Rapid Response Against Emerging Coronaviruses: MERS-CoV Serologic and Antigenic Relationships in Vaccine Design
Sudhakar Agnihothram 1,*, Robin Gopal 3,*, Boyd L. Yount Jr 1, Eric F. Donaldson 1, Vineet D. Menachery 1, Rachel L. Graham 1, Trevor D. Scobey 1, Lisa E. Gralinski 1, Mark R. Denison 2, Maria Zambon 3 and Ralph S. Baric 1,?
Author Affiliations: <SUP>1</SUP>Departments of Epidemiology and Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599 <SUP>2</SUP>Departments of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232 <SUP>3</SUP>Viral Zoonosis Unit, Public Health of England, London NW9 5HT
?Corresponding Author`s Contact Information. Ralph S. Baric, Ph.D. Professor, Department of Microbiology and Immunology, 3304 Michael Hooker Research Building, Campus Box 7435, Chapel Hill, NC 27599 -7435, Ph: 919-966-3895, Email: rbaric@email.unc.edu
* These two authors contributed equally to this work.
<CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit609 </CITE>First published online: November 18, 2013
Abstract
Background.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 causing Severe Acute Respiratory Disease and pneumonia, with ∼44% mortality in 136 cases till date. Design of vaccines to limit the virus spread or diagnostics to track newly emerging strains requires knowledge of antigenic and serological relationships of MERS-CoV to other coronaviruses.
Methods.
Using synthetic genomics and Venezuelan Equine Encephalitis Virus replicons (VRPs) expressing S and N proteins from MERS-CoV and other human and bat CoV`s, we characterize the antigenic (using western blots and ELISA) and serological responses (using Neutralization Assays) against two MERS-CoV isolates in comparison with other human and bat coronaviruses.
Results.
Serologic and neutralization responses against the S glycoprotein were primarily strain specific with very low level cross reactivity within, or across subgroups. Coronaviruses N proteins within, but not across subgroups, share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using MERS-CoV patient (NA 01) convalescent serum, and human serum to SARS-CoV, NL63 and OC43.
Conclusions.
Vaccine design for emerging coronaviruses should involve chimeric S protein containing neutralizing epitopes from multiple virus strains across subgroups, to reduce immune pathology, and diagnostic platform should include a panel of N and S proteins from phylogenetically distinct coronaviruses.
Received August 16, 2013. Revision received October 6, 2013. Accepted October 11, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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Platform Strategies for Rapid Response Against Emerging Coronaviruses: MERS-CoV Serologic and Antigenic Relationships in Vaccine Design
Sudhakar Agnihothram 1,*, Robin Gopal 3,*, Boyd L. Yount Jr 1, Eric F. Donaldson 1, Vineet D. Menachery 1, Rachel L. Graham 1, Trevor D. Scobey 1, Lisa E. Gralinski 1, Mark R. Denison 2, Maria Zambon 3 and Ralph S. Baric 1,?
Author Affiliations: <SUP>1</SUP>Departments of Epidemiology and Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599 <SUP>2</SUP>Departments of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232 <SUP>3</SUP>Viral Zoonosis Unit, Public Health of England, London NW9 5HT
?Corresponding Author`s Contact Information. Ralph S. Baric, Ph.D. Professor, Department of Microbiology and Immunology, 3304 Michael Hooker Research Building, Campus Box 7435, Chapel Hill, NC 27599 -7435, Ph: 919-966-3895, Email: rbaric@email.unc.edu
* These two authors contributed equally to this work.
<CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit609 </CITE>First published online: November 18, 2013
Abstract
Background.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 causing Severe Acute Respiratory Disease and pneumonia, with ∼44% mortality in 136 cases till date. Design of vaccines to limit the virus spread or diagnostics to track newly emerging strains requires knowledge of antigenic and serological relationships of MERS-CoV to other coronaviruses.
Methods.
Using synthetic genomics and Venezuelan Equine Encephalitis Virus replicons (VRPs) expressing S and N proteins from MERS-CoV and other human and bat CoV`s, we characterize the antigenic (using western blots and ELISA) and serological responses (using Neutralization Assays) against two MERS-CoV isolates in comparison with other human and bat coronaviruses.
Results.
Serologic and neutralization responses against the S glycoprotein were primarily strain specific with very low level cross reactivity within, or across subgroups. Coronaviruses N proteins within, but not across subgroups, share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using MERS-CoV patient (NA 01) convalescent serum, and human serum to SARS-CoV, NL63 and OC43.
Conclusions.
Vaccine design for emerging coronaviruses should involve chimeric S protein containing neutralizing epitopes from multiple virus strains across subgroups, to reduce immune pathology, and diagnostic platform should include a panel of N and S proteins from phylogenetically distinct coronaviruses.
Received August 16, 2013. Revision received October 6, 2013. Accepted October 11, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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