“Vaccines have saved more lives than any other invention in human history”, explained J. Joseph Kim, Ph.D., president and CEO of Inovio Pharmaceuticals. “Conventional vaccines have been successfully used against the lower hanging fruit in terms of disease, and more complex diseases such as cancer represent both opportunities and challenges for DNA vaccines."
According to Dr. Kim, one of the biggest hurdles for DNA vaccines has been inducing sufficiently high immune responses for effective vaccination. “There are two issues at stake,” he said. “The first is to make plasmids more ‘people-friendly’ to optimize their expression once in the cell, and the second is to optimize the rapid transfer of the DNA across the cell membrane to avoid degradation by endonucleases.
Inovio’s approach in this area includes informatically assisted optimization of the coding sequence to expand immunogenicity across multiple targets and boost expression levels of immunogens in target cells, and to improve the delivery of the plasmid DNA into host cells to minimize exposure to extracellular nucleases. The development of one of Inovio’s candidate high-grade cervical dysplasia vaccines, VGX-3100, encoding the HPV16 and HPV18 E6/E7 antigens, incorporated a combination of these features to increase vaccine antigen immune potency.
“The VGX-3100 vaccine was developed using our SynCon platform and includes highly efficient leader and Kozak sequences,” said Dr. Kim. “We also introduced an endoproteolytic cleavage site to improve protein folding and cytotoxic T lymphocyte processing.”
In addition, Inovio has developed an electroporation-based delivery system that, according to Dr. Kim, allows for more efficient and safe targeting of the antigenic sequence to the target cell. “A low voltage electrical field is applied at the site of vaccine injection, causing the cell membranes to transiently realign into a more porous state,” he explained, adding that electroporation is the most efficient and safe mode of delivery of nucleic acids, requiring no additional chemicals, preservatives, or adjuvants.
Looking to the future, “Electroporation is not a static technology,” continued Dr. Kim. “We are developing new devices, referred to as surface electroporators, that sit on the surface of the skin, and a piezo-electric-based system that doesn’t even require contact with the skin.”