Abstract
Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.
Highlights
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a positive-sense, single-stranded RNA coronavirus that infects the lower and upper respiratory tract, causing a viral pneumonia characterized by acute respiratory symptoms, such as fever, aches, shortness of breath, sore throat, cough, diarrhea, and vomiting [1]
The urgent need for accelerated vaccine development has become critical in light of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a betacoronavirus related to MERS-CoV
We evaluated the efficacy of our previously described synthetic MERS DNA vaccine [6], which had been studied in nonhuman primates (NHPs) using an i.m. 3-dose immunization regimen
Summary
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a positive-sense, single-stranded RNA coronavirus that infects the lower and upper respiratory tract, causing a viral pneumonia characterized by acute respiratory symptoms, such as fever, aches, shortness of breath, sore throat, cough, diarrhea, and vomiting [1]. Since 2012, there have been 2566 laboratory-confirmed cases and 882 MERS-CoV– associated deaths (34.4% case fatality rate) [2]. The 2015 South Korean outbreak originated from a single traveler who returned home from the Middle East. 186 people were infected during the South Korean outbreak, with 36 MERS-associated fatalities [3] and a significant impact on the healthcare system. This outbreak highlights the importance of rapid infection control for emerging coronaviruses and other infectious diseases. The urgent need for accelerated vaccine development has become critical in light of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a betacoronavirus related to MERS-CoV
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