Inovio Pharmaceuticals, Inc. announced that its novel dMAb antibody and DNA vaccine targeting the chikungunya virus (CHIKV) provided 100 per cent protection against a lethal virus challenge in mice. This breakthrough data was published in the latest issue of The Journal of Infectious Diseases in a paper, “Rapid and long-term immunity elicited by DNA encoded antibody prophylaxis and DNA vaccination against Chikungunya virus,” prepared by Inovio authors and their academic collaborators. While conventional vaccine and marketed monoclonal antibody technologies have shown limited ability to provide an effective solution to CHIKV to date, Inovio’s DNA vaccine and dMAb products show potential, separately and in combination, to offer immediate and long term protection to large populations from CHIKV infection.
Over the years, CHIKV outbreaks have occurred in Africa, Asia, Europe, and throughout the Indian and Pacific Oceans, with local transmission in over 43 countries infecting millions of people. In late 2013, CHIKV was found for the first time in the Americas on islands in the Caribbean and spreading to other parts of the western hemisphere, including the United States. Along with a dramatic increase in cases and geographic spread of CHIKV infection and disease there has been a reported increase in morbidity and mortality, suggesting increased virulence. The concern for even greater potential global outbreaks underscores the need for targeted anti-viral interventions.
Inovio previously published that its SynCon DNA vaccine for CHIKV provided durable 100 per cent protection in mice. In this study, a single intramuscular injection of a DNA plasmid encoding a monoclonal antibody targeting CHIKV protected mice from a lethal dose of the virus. The protection expressed by these dMAb antibodies was very rapid, with 100 per cent survival in mice challenged with lethal enhanced CHIKV disease as early as two days after dMAb product administration. In comparison, vaccine-driven protection can take weeks to months to reach peak efficacy levels, but providing better long term protection compared to a dMAb product. Inovio’s study demonstrates that its CHIKV dMAb antibody and DNA vaccine could be used as an ideal combination to provide both rapid short-term as well as long-term protection.
Dr. J. Joseph Kim, Inovio’s president & CEO, said, “This study is significant for two reasons. First, this is our third published study (two previous in HIV and dengue) demonstrating the protective efficacy of our dMAb products. Inovio is rapidly building its dMAb product development program targeting cancer and infectious diseases. Notably, DARPA is providing us over $56 million to specifically develop dMAb products against influenza, antibiotic-resistant bacteria, and Ebola.
“Second, this study demonstrates that Inovio’s dMAb products and DNA vaccines could be a powerful combination to provide robust immediate and long term protection not only for CHIKV but also other infectious diseases. Inovio is the only organisation to report such results in any disease by using a DNA-based monoclonal antibody, with published preclinical data in dengue as well, and we now are creating Zika, MERS, and Ebola dMAb products. Our MERS and Ebola vaccines are in phase I clinical studies and we will advance our Zika vaccine to phase I before year end. We also aim to test further combinations.”
Chikungunya does not often result in death, but the symptoms can be severe and disabling and include extreme pain, headache, muscle pain, joint swelling, or rash. The chikungunya virus is carried by the same mosquito species which carry Zika, dengue and West Nile virus (WNV). Inovio previously published robust immunogenicity and challenge protection data for its SynCon CHIKV, dengue, and WNV vaccine candidates. Inovio’s chikungunya program builds on its extensive preclinical development experience with various mosquito-borne viruses.
Unlike conventional monoclonal technology, which involves constructing protein-based antibodies and manufacturing them in cell culture in a complex and costly process, Inovio’s patent-protected DNA-based monoclonal antibody technology encodes the DNA sequence for a specific monoclonal antibody in a highly optimised plasmid, which would be delivered directly into a subject’s arm using electroporation. Cells in the body would then produce the encoded monoclonal antibody molecules, with intended functional activity including high antigen-binding and neutralization capabilities against the targeted disease. Monoclonal antibodies offer the benefit of inducing a rapid onset of the immune response. The current monoclonal antibody product market is well over $50 billion. Overall, Inovio’s dMAb technology may provide clear advantages over conventional monoclonal antibody technology, including faster development, easier product manufacturing, and more favorable pharmacokinetics.