By Deborah Borfitz
September 19, 2011 | In as few as five years, all of the major shortcomings of conventional vaccines will start to vanish as the first DNA-based vaccines hit the market. The vaccines will be remarkably safe and tolerable, easily modified, and cheap to produce in a manufacturing process akin to brewing beer. They’ll also have a long shelf life, maintaining their fidelity even in steamy tropical climates. The development process itself will better integrate scientific inquiry with trial design, so that subsequent vaccines improve with the regularity of an iPhone upgrade.
At least that’s the intention of Inovio Pharmaceuticals CEO Joseph Kim and David Weiner, chairman of the company’s scientific advisory board. Weiner is Kim’s former PhD advisor at the University of Pennsylvania and a top pioneer in the vaccine field. The two men co-founded VGX Pharmaceuticals, which merged with publicly held Inovio in June 2009. They’re now leading development of therapeutic DNA-based vaccines for cervical cancer, acute and chronic myeloid leukemia, hepatitis C, and HIV infection as well as a preventive vaccine for HIV and a universal flu shot.
Globally patented “electroporation” technology for delivering vaccine to cells is the key piece of technology making this all possible, says Kim, who for over nine years led manufacturing and process development of vaccine programs at Merck & Co. The technology didn’t venture out of the laboratory setting until about six years ago. In terms of immune response, electroporation-based DNA delivery has been shown to facilitate immune responses comparable or superior to other vaccine platforms like viral vectors and live or inactivated virus vaccines.
Inovio’s universal flu vaccine further utilizes its patented “synthetic consensus” (SynCon) vaccine design that incorporates a string of “decoy” DNA sequences to trigger an immune response to both known and newly emergent influenza viruses of a targeted subtype (such as H5N1 or H1N1). Essentially, Inovio is creating a “sketch [of divergent viruses] for immune soldiers in the body to recognize,” says Kim. It’s an admittedly “lofty goal,” but the one-size-fits-all vaccine had a strong showing in animal and early human studies. Last year, Inovio’s vaccine strategy received $3 million in support via a National Institutes of Health Director’s Transformative Research Award.
Traditional vaccines have successfully hit easier targets ranging from the prevention of polio to the human papillomavirus (HPV) using a half-century-old development technique: artificially growing viruses in an egg-based medium. “It’s like driving a Model T,” says Kim. Diseases lacking vaccines are more complex, often caused by rapidly changing viruses or bacteria that have eluded this conventional approach.
A large number of companies are nonetheless pursuing the established vaccine development route for these trickier conditions, with much of the activity focused on HIV prevention, reports Stanley Plotkin, MD, a world-renowned vaccine pioneer who helped develop the rubella and rabies vaccine and now serves on Inovio’s scientific advisory board.
Inovio’s tactic is to immunize with only the genetic code for a virus’s proteinaceous parts. This opens up flu vaccination to the 10%-15% of Americans considered immune-compromised who cannot tolerate a live replicating virus vaccine. DNA-based vaccines, Kim explains, “uses the body’s own machinery to generate [the] vaccine.” It also eliminates the chance introduction of hard-to-detect “impurities,” notably preservatives and adjuvants that underlie public vaccination fears. Moreover, because of the way DNA-based vaccines generate immune response in the T-cell realm, they can be used to treat as well as prevent disease.
After a decade of efforts, Inovio now has eight vaccines in clinical trials. Five of the products are still in phase I trials. The other three, all therapeutic vaccines, entered phase II testing in the first quarter of 2011. If successful, they could hit the market as early as 2016, says Kim. Among them is a flagship product the company calls VGX-3100 for treating people already infected with HPV, the cause of 99% of all cervical cancers. Inovio’s hepatitis C remedy is being tested in conjunction with standard drug therapy. Treatment vaccines are a wholly untapped market outside of Dendreon’s Provenge for treating prostate cancer, Kim notes.
The only other company with advanced clinical stage projects of this sort is publicly traded Vical, with 30 completed clinical trials. Among those currently underway is a cancer immunotherapy trial for metastatic melanoma—the only phase III vaccine study utilizing DNA technology.
But, to date, Inovio has “come closest” to overcoming the major challenges of the DNA platform, says Plotkin. These include inducing antibodies as well as cellular immunity, achieving responses with reasonable amounts of DNA (preferably without a boost from another vaccine platform), demonstrating clinical efficacy, and delivering the DNA in a well tolerated way.
Worldwide, thousands of patients have been safely vaccinated with experimental DNA-based vaccines, says Kim. Thus far, there have been no safety signals. Adverse events have been limited primarily to minor redness and swelling at the injection site. But, like all novel approaches, DNA vaccines require a more cautious approach to regulatory and informed consent processes.
Inovio has been separately working toward a vaccine for malaria, the biggest of the parasitic diseases, thanks to a two-year-old partnership with the Bill & Melinda Gates Foundation’s Malaria Vaccine Initiative. Human testing could begin in another 12 to 18 months, says Kim.