Inovio Pharmaceuticals, Inc. announced that preclinical testing of a DNA synthetic vaccine for the virulent Middle East Respiratory Syndrome coronavirus (MERS) induced robust and durable immune responses, demonstrating the potential for a SynCon® DNA vaccine to prevent and treat this deadly virus.
Since 2012, when the virus was first identified, 153 cases from nine Middle Eastern countries have been reported and, alarmingly, 42% of these cases have been fatal. MERS is similar to the SARS virus which infected 8,000 people several years ago. MERS differs from SARS in that it appears to be less contagious, but MERS is almost five times as fatal as SARS, which killed 10% of those infected. There is no vaccine or effective treatment for MERS.
In this study, DNA vaccine constructs targeting multiple MERS antigens were generated using Inovio's SynCon® vaccine platform. These SynCon constructs were administered via Inovio's CELLECTRA® electroporation-based delivery technology. The vaccine constructs were observed to induce strong neutralizing antibodies and broad CD8+ T cells in mice. These findings are vital given the importance of neutralizing antibodies in preventing infection and the role T cells play in clearing infection by killing cells that harbor the virus.
Dr. J. Joseph Kim, Inovio's President and CEO, said, "Our SynCon® platform has again generated a synthetic vaccine candidate that shows promise for providing a treatment where there is none. With human data showing the powerful killing effect of T cells generated by our vaccine for HIV and our therapy for HPV-associated cervical dysplasia and various cancers, we look forward to providing Inovio's answer to MERS, a deadly infectious disease that has unknown pandemic potential. What's even more impressive about our candidate vaccine is that it is designed with the goal to universally protect against multiple strains of MERS, which has been shown to have diverse genetic variants. With appropriate external funding, this product could become an effective shield against this deadly virus."
To begin the study, a consensus MERS "spike" protein vaccine construct was created based on multiple strains of the MERS virus. Inovio's MERS DNA vaccine was immunogenic in mice and seroconversion, or the development of detectable specific antibodies in the blood as a result of immunization, was observed in all animals. Furthermore, the antibodies generated by the vaccine in 100% of mice (20 of 20) were able to neutralize or completely block actual infection of MERS virus in the cells, demonstrating the protective potential of this vaccine. In contrast, none of the unvaccinated mice in the control group (10) generated neutralizing antibodies.
Researchers also observed that vaccination was highly T-cell immunogenic, generating robust and broad T cell responses as extensively analyzed by the standardized T cell ELISPOT assay. The vaccine produced robust CD8+ and CD4+ T cell responses against multiple epitopes of the MERS spike protein. This increased diversity and magnitude of cellular responses may be critical for effectively mitigating MERS infection.