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

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.

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

“…Another encouraging study also reported a partial protection in NHPs using only DNA vaccine based on the consensus sequence of the S gene . This vaccine was delivered to Rhesus macaques in 3 homologous DNA vaccinations, with 3‐week intervals.…”

“…Most importantly, this vaccine was the first to undergo camel immunization. Two of 3 vaccinated dromedary camels developed S‐specific antibodies (Table ) . Overall, this vaccine induced high titer nAb in mice, camels, and monkeys and has now advanced to human clinical trials (discussed in the next section).…”

Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

“…Most candidate vaccines are still being evaluated in animal models. They have generally targeted the spike protein of MERS-CoV and are recombinant virus, subunit, DNA, or virus-like vector vaccines ( 60 , 63 – 67 ). One live-attenuated MERS-CoV candidate vaccine is in early development ( 66 ).…”

“…Experimental MERS-CoV infection studies and vaccine studies of a small number of dromedaries have been conducted in large animal Biosafety Level 3 facilities in the United States and overseas ( 19 ). In addition, 3 doses of a DNA vaccine containing the MERS-CoV spike protein induced humoral immunity in dromedaries ( 60 ). In a recent study, a modified vaccinia virus Ankara vaccine that expresses the MERS-CoV spike protein was administered intranasally and intramuscularly to dromedaries; when challenged intranasally with MERS-CoV, vaccinated dromedaries had fewer signs of respiratory infection and lower MERS-CoV titers in the upper respiratory tract compared with unvaccinated dromedaries ( 76 ).…”

Middle East respiratory syndrome: current status and future prospects for vaccine development

“…An optimized DNA vaccine encoding full-length S protein of MERS-CoV was able to elicit antigen-specific neutralizing antibodies in mice, camels and rhesus macaques (non-human primates, NHPs), with six of the eight vaccinated macaques showing no radiographic evidence of infiltration after MERS-CoV challenge. Interestingly, potent antigen-specific cellular immune responses were induced in the immunized macaques, suggesting that T cell responses may also play a role in MERS-CoV protection [25]. Inovio Pharmaceuticals Inc., in collaboration with GeneOne Life Science, will perform a Phase I clinical trial for this DNA-based vaccine [26].…”