A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.
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.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Karuppiah
K
Muthumani
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.
Darryl
D
Falzarano
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Emma L
EL
Reuschel
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Colleen
C
Tingey
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Seleeke
S
Flingai
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Daniel O
DO
Villarreal
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Megan
M
Wise
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Ami
A
Patel
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Abdullah
A
Izmirly
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Abdulelah
A
Aljuaid
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Alecia M
AM
Seliga
Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
Geoff
G
Soule
Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
Matthew
M
Morrow
Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
Kimberly A
KA
Kraynyak
Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
Amir S
AS
Khan
Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
Dana P
DP
Scott
Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
Friederike
F
Feldmann
Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
Rachel
R
LaCasse
Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
Kimberly
K
Meade-White
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Atsushi
A
Okumura
Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Kenneth E
KE
Ugen
Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
Niranjan Y
NY
Sardesai
Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
J Joseph
JJ
Kim
Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
Gary
G
Kobinger
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.
Heinz
H
Feldmann
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA. dbweiner@mail.med.upenn.edu.
David B
DB
Weiner
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002162:Camelus; D008253:Macaca mulatta; D051379:Mice; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*; D019444:Vaccines, DNA / Q000627:therapeutic use*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA