๐ A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates
ยฉ 2015 American Association for the Advancement of Science. 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 coupledwith 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 againstMERS-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. Vaccinatedmacaqueswere 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.
keywords
๐ severe acute (1373)
๐ syndrome coronavirus (1074)
๐ spike protein (353)
๐ neutralizing antibodies (122)
๐ human coronavirus (623)
๐ rhesus macaques (12)
๐ respiratory syndrome (2004)
๐ acute respiratory (1734)
author
๐ค Muthumani, Karuppiah
๐ค Falzarano, Darryl
๐ค Reuschel, Emma L.
๐ค Tingey, Colleen
๐ค Flingai, Seleeke
๐ค Villarreal, Daniel O.
๐ค Wise, Megan
๐ค Patel, Ami
๐ค Izmirly, Abdullah
๐ค Aljuaid, Abdulelah
๐ค Seliga, Alecia M.
๐ค Soule, Geoff
๐ค Morrow, Matthew
๐ค Kraynyak, Kimberly A.
๐ค Khan, Amir S.
๐ค Scott, Dana P.
๐ค Feldmann, Friederike
๐ค LaCasse, Rachel
๐ค Meade-White, Kimberly
๐ค Okumura, Atsushi
๐ค Ugen, Kenneth E.
๐ค Sardesai, Niranjan Y.
๐ค Kim, J. Joseph
๐ค Kobinger, Gary
๐ค Feldmann, Heinz
๐ค Weiner, David B.
year
โฐ 2015
issn
๐ 19466242 19466234
volume
7
number
301
page
citedbycount
71
download
๐ [BibTeX]