A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates

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. Weiner

doi:10.1126/scitranslmed.aac7462

Research ArticleInfectious Disease

A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates

Karuppiah Muthumani¹,*,
Darryl Falzarano²,*,†,
Emma L. Reuschel¹,
Colleen Tingey¹,
Seleeke Flingai¹,
Daniel O. Villarreal¹,
Megan Wise¹,
Ami Patel¹,
Abdullah Izmirly¹,
Abdulelah Aljuaid¹,
Alecia M. Seliga¹,
Geoff Soule³,
Matthew Morrow⁴,
Kimberly A. Kraynyak⁴,
Amir S. Khan⁴,
Dana P. Scott⁵,
Friederike Feldmann⁵,
Rachel LaCasse⁵,
Kimberly Meade-White⁵,
Atsushi Okumura⁶,
Kenneth E. Ugen⁷,
Niranjan Y. Sardesai⁴,
J. Joseph Kim⁴,
Gary Kobinger³,
Heinz Feldmann² and
David B. Weiner¹,‡

¹Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
²Laboratory 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.
³Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
⁴Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
⁵Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
⁶Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
⁷Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.

↵‡Corresponding author. E-mail: dbweiner{at}mail.med.upenn.edu

↵* These authors contributed equally to this work.
↵† Present address: Vaccine and Infectious Disease Organization–International Vaccine Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.

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Science Translational Medicine 19 Aug 2015:
Vol. 7, Issue 301, pp. 301ra132
DOI: 10.1126/scitranslmed.aac7462

Karuppiah Muthumani

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Darryl Falzarano

2Laboratory 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.

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Emma L. Reuschel

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Colleen Tingey

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Seleeke Flingai

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Daniel O. Villarreal

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Megan Wise

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Ami Patel

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Abdullah Izmirly

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Abdulelah Aljuaid

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Alecia M. Seliga

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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Geoff Soule

3Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.

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Matthew Morrow

4Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

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Kimberly A. Kraynyak

4Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

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Amir S. Khan

4Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

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Dana P. Scott

5Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.

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Friederike Feldmann

5Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.

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Rachel LaCasse

5Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.

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Kimberly Meade-White

5Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.

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Atsushi Okumura

6Department of Microbiology, University of Washington, Seattle, WA 98195, USA.

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Kenneth E. Ugen

7Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.

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Niranjan Y. Sardesai

4Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

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J. Joseph Kim

4Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

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Gary Kobinger

3Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.

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Heinz Feldmann

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David B. Weiner

1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

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For correspondence: dbweiner@mail.med.upenn.edu

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Emerging vaccines

Public outcry drives vaccine research during outbreaks of emerging infectious disease, but public support for vaccine development dries up when the outbreaks are resolved, frequently leaving promising vaccine candidates sitting on the shelf. DNA vaccines, with their potential for rapid large-scale production, may help overcome this hurdle. Muthumani et al. report the development of a synthetic DNA vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) that induces neutralizing antibodies in mice, macaques, and camels—natural hosts of MERS-CoV. Indeed, macaques vaccinated with this DNA vaccine were protected from viral challenge. These promising results support further development of DNA vaccines for emerging infections.

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A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates

Emerging vaccines

Science Translational Medicine

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