A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.
Identifieur interne : 001502 ( PubMed/Corpus ); précédent : 001501; suivant : 001503A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.
Auteurs : Karuppiah Muthumani ; Darryl Falzarano ; Emma L. Reuschel ; Colleen Tingey ; Seleeke Flingai ; Daniel O. Villarreal ; Megan Wise ; Ami Patel ; Abdullah Izmirly ; Abdulelah Aljuaid ; Alecia M. Seliga ; Geoff Soule ; Matthew Morrow ; Kimberly A. Kraynyak ; Amir S. Khan ; Dana P. Scott ; Friederike Feldmann ; Rachel Lacasse ; Kimberly Meade-White ; Atsushi Okumura ; Kenneth E. Ugen ; Niranjan Y. Sardesai ; J Joseph Kim ; Gary Kobinger ; Heinz Feldmann ; David B. WeinerSource :
- Science translational medicine [ 1946-6242 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- chemical , therapeutic use : Vaccines, DNA.
- Animals, Camelus, Macaca mulatta, Mice.
Abstract
First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.
DOI: 10.1126/scitranslmed.aac7462
PubMed: 26290414
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pubmed:26290414Le document en format XML
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<author><name sortKey="Muthumani, Karuppiah" sort="Muthumani, Karuppiah" uniqKey="Muthumani K" first="Karuppiah" last="Muthumani">Karuppiah Muthumani</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name>
<affiliation><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Reuschel, Emma L" sort="Reuschel, Emma L" uniqKey="Reuschel E" first="Emma L" last="Reuschel">Emma L. Reuschel</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tingey, Colleen" sort="Tingey, Colleen" uniqKey="Tingey C" first="Colleen" last="Tingey">Colleen Tingey</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Flingai, Seleeke" sort="Flingai, Seleeke" uniqKey="Flingai S" first="Seleeke" last="Flingai">Seleeke Flingai</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Villarreal, Daniel O" sort="Villarreal, Daniel O" uniqKey="Villarreal D" first="Daniel O" last="Villarreal">Daniel O. Villarreal</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wise, Megan" sort="Wise, Megan" uniqKey="Wise M" first="Megan" last="Wise">Megan Wise</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Izmirly, Abdullah" sort="Izmirly, Abdullah" uniqKey="Izmirly A" first="Abdullah" last="Izmirly">Abdullah Izmirly</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Aljuaid, Abdulelah" sort="Aljuaid, Abdulelah" uniqKey="Aljuaid A" first="Abdulelah" last="Aljuaid">Abdulelah Aljuaid</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Seliga, Alecia M" sort="Seliga, Alecia M" uniqKey="Seliga A" first="Alecia M" last="Seliga">Alecia M. Seliga</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Soule, Geoff" sort="Soule, Geoff" uniqKey="Soule G" first="Geoff" last="Soule">Geoff Soule</name>
<affiliation><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Morrow, Matthew" sort="Morrow, Matthew" uniqKey="Morrow M" first="Matthew" last="Morrow">Matthew Morrow</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kraynyak, Kimberly A" sort="Kraynyak, Kimberly A" uniqKey="Kraynyak K" first="Kimberly A" last="Kraynyak">Kimberly A. Kraynyak</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Khan, Amir S" sort="Khan, Amir S" uniqKey="Khan A" first="Amir S" last="Khan">Amir S. Khan</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Meade White, Kimberly" sort="Meade White, Kimberly" uniqKey="Meade White K" first="Kimberly" last="Meade-White">Kimberly Meade-White</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA 98195, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ugen, Kenneth E" sort="Ugen, Kenneth E" uniqKey="Ugen K" first="Kenneth E" last="Ugen">Kenneth E. Ugen</name>
<affiliation><nlm:affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name>
<affiliation><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name>
<affiliation><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA. dbweiner@mail.med.upenn.edu.</nlm:affiliation>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.</title>
<author><name sortKey="Muthumani, Karuppiah" sort="Muthumani, Karuppiah" uniqKey="Muthumani K" first="Karuppiah" last="Muthumani">Karuppiah Muthumani</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name>
<affiliation><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Reuschel, Emma L" sort="Reuschel, Emma L" uniqKey="Reuschel E" first="Emma L" last="Reuschel">Emma L. Reuschel</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tingey, Colleen" sort="Tingey, Colleen" uniqKey="Tingey C" first="Colleen" last="Tingey">Colleen Tingey</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Flingai, Seleeke" sort="Flingai, Seleeke" uniqKey="Flingai S" first="Seleeke" last="Flingai">Seleeke Flingai</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Villarreal, Daniel O" sort="Villarreal, Daniel O" uniqKey="Villarreal D" first="Daniel O" last="Villarreal">Daniel O. Villarreal</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wise, Megan" sort="Wise, Megan" uniqKey="Wise M" first="Megan" last="Wise">Megan Wise</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Izmirly, Abdullah" sort="Izmirly, Abdullah" uniqKey="Izmirly A" first="Abdullah" last="Izmirly">Abdullah Izmirly</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Aljuaid, Abdulelah" sort="Aljuaid, Abdulelah" uniqKey="Aljuaid A" first="Abdulelah" last="Aljuaid">Abdulelah Aljuaid</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Seliga, Alecia M" sort="Seliga, Alecia M" uniqKey="Seliga A" first="Alecia M" last="Seliga">Alecia M. Seliga</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Soule, Geoff" sort="Soule, Geoff" uniqKey="Soule G" first="Geoff" last="Soule">Geoff Soule</name>
<affiliation><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Morrow, Matthew" sort="Morrow, Matthew" uniqKey="Morrow M" first="Matthew" last="Morrow">Matthew Morrow</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kraynyak, Kimberly A" sort="Kraynyak, Kimberly A" uniqKey="Kraynyak K" first="Kimberly A" last="Kraynyak">Kimberly A. Kraynyak</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Khan, Amir S" sort="Khan, Amir S" uniqKey="Khan A" first="Amir S" last="Khan">Amir S. Khan</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Meade White, Kimberly" sort="Meade White, Kimberly" uniqKey="Meade White K" first="Kimberly" last="Meade-White">Kimberly Meade-White</name>
<affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA 98195, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ugen, Kenneth E" sort="Ugen, Kenneth E" uniqKey="Ugen K" first="Kenneth E" last="Ugen">Kenneth E. Ugen</name>
<affiliation><nlm:affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name>
<affiliation><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name>
<affiliation><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name>
<affiliation><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name>
<affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA. dbweiner@mail.med.upenn.edu.</nlm:affiliation>
</affiliation>
</author>
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<term>Antibodies, Viral (immunology)</term>
<term>Camelus</term>
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<term>Mice</term>
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<front><div type="abstract" xml:lang="en">First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.</div>
</front>
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<Abstract><AbstractText>First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.</AbstractText>
<CopyrightInformation>Copyright © 2015, American Association for the Advancement of Science.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Muthumani</LastName>
<ForeName>Karuppiah</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Falzarano</LastName>
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