436. Developing a Synthetic DNA Vaccine for an Emerging Pathogen - Middle East Respiratory Syndrome

Background: Middle East Respiratory Syndrome (MERS) was first reported in 2012 in Saudi Arabia when a patient died from severe respiratory disease caused by a novel betacorona virus, MERS-CoV. Through November 2015, there have been 1618 confirmed global cases of MERS-CoV infection and 579 deaths reported to the World Health Organization (WHO). Currently, no vaccine or specific treatment is available and patients are treated with supportive care based on their clinical condition. While most MERS cases occur in and around Saudi Arabia, the recent outbreak in Korea highlights the potential for this disease to spread beyond the immediate region. A vaccine is needed to prevent future disease caused by MERS-CoV.Methods: A synthetic DNA MERS vaccine was generated using a consensus sequence of the MERS spike protein. Mice, dromedary camels, and non-human primates (NHP) were immunized with MERS-vaccine by intramuscular injection followed by electroporation. Cellular immune responses were measured by flow cytometry and IFNγ ELISpot. Humoral immune responses were measured by ELISA and neutralizing antibody (nAb) assay. Following immunization, NHPs were challenged with infectious MERS-CoV (EMC/2012) and monitored for signs of infection by clinical scoring and examinations. Viral load was measured by qRT-PCR and tissue sections were stained with Hu0026E.Results: Immunization of mice with MERS-vaccine induced strong humoral and cellular responses. Mice produced strong binding antibody (bAb) titers and nAb titers. A strong, polyfunctional, CD4 and CD8 T cell response was detected against multiple epitopes across the MERS spike protein. Immunization of dromedary camels induced the production of MERS spike specific antibodies and nAbs. Immunization of NHPs induced strong bAb titers and nAb titers and a strong CD4 and CD8 T cell response. NHPs immunized with multiple vaccination regimens were also protected from signs of disease upon challenge with infectious MERS-CoV and showed a greater than 3 log reduction in viral load after challenge compared to unvaccinated animals.Conclusions: A consensus DNA MERS-vaccine was able to generate both a strong T cell and neutralizing antibody response in multiple animal models, including camels, a natural host for MERS-CoV and a probable source of human infection. MERS-vaccine was also able to protect NHPs from an infectious MERS-CoV challenge. These results demonstrate the promise of this consensus DNA MERS-vaccine as a candidate for vaccine development.