By Dr. John Lewis
Like most of us, Dr. John Lewis had different plans for 2020.
By the end of 2019, his biotechnology company, Entos Pharmaceuticals, was generating a lot of buzz for its proprietary drug delivery platform. The platform, known as Fusogenix, uses cutting-edge nanotechnology to bring targeted medicines directly to specific cells in the body—a process that has the potential to generate new and better ways of treating cancer and other chronic diseases.
Dr. Lewis, a professor in the Department of Experimental Oncology at the University of Alberta, was busy establishing partnerships to support this interest in Fusogenix and expanding his own research program on cancer metastasis when the COVID-19 pandemic arrived and upended all of our lives.
Knowing they could help, Dr. Lewis and his team felt the call of duty to expand their work.
“We already knew that our drug delivery platform would work for vaccine development, so we made the decision to lean in and focus on COVID-19,” he says. “It has been full steam ahead ever since.”
For months now, our collective hopes have been pinned to the development of a successful vaccine as our best chance to get the global pandemic under control. The benefit of vaccination in general is that the process triggers an immune response without causing disease: the vaccine essentially serves as a “wanted poster” that primes the immune system to be on the lookout for the potential intruder (pathogen). The poster, however, is also like a “cheat sheet” that tells the body how to prepare very specific equipment to use on the intruder if it arrives.
With traditional vaccines, this effect is typically created by using a piece of the target pathogen (or the whole thing in a deactivated form) to act as that wanted poster/cheat sheet. The vaccine will actually contain that harmless bit of pathogen, which the immune system can then wave around as a warning. But Dr. Lewis’s team is working on a brand new approach—called a DNA vaccine—that is more like giving a sophisticated “paint-by-numbers” version of that wanted poster directly to our cells. Instead of receiving the actual piece of pathogen to wave around, the cells that receive the paint-by-numbers poster will fill in the details to create harmless replicas of those pathogen pieces on their own. Using those replicas to warn the body about a potential intruder is, like traditional vaccines, an effective way to build its defenses.
The key to this type of vaccine is finding a way to deliver the DNA directly into host cells successfully. That paint-by-numbers poster is created by using snippets of DNA for fragments of the target pathogen (hence the “DNA vaccine” moniker), but it only works if it can be delivered in a way that the cells can accept, read, and act on. This is where nanotechnology comes in—which, for Dr. Lewis’s team, is the Fusogenix delivery platform. It is capable of bringing the DNA exactly where it needs to go without damaging the host cell along the way.
There are a number of DNA vaccines against COVID-19 in development across Canada and around the world, and that doesn’t surprise Dr. Lewis. He says there is a lot of innovation taking place right now, which is good news for all of us. Yet, he also understands how the novelty of the technology and the inescapable emphasis on rapid development could make people nervous.
“The design and implementation of our vaccine candidates and trials are by the book,” he explains, emphasizing that his team is in no way cutting corners or risking safety in order to speed things up. “You see headlines about how it normally takes a decade to develop a vaccine—and that’s true, but that’s partly because a number of things would normally be happening in sequence rather than in parallel. For example, we will have overlapping Phase 1 and Phase 2 clinical trials, but in an adaptive way that lets us learn and deal with everything we would have had to learn and deal with if we had run those trials back to back instead. And our preclinical work was done first, which allowed us to narrow our list of prototypes from 24 down to the two with the greatest potential for success, so everything has still been very meticulous.”
The team is preparing to launch the Phase 1 clinical trial later this month (November 2020) at the Canadian Centre for Vaccinology in Halifax, Nova Scotia, where the first group of volunteers has already been recruited to participate. These volunteers will receive an intramuscular shot in the arm, much like other vaccines, and will then be monitored closely. Based on their work to date with animal studies, Dr. Lewis says their data suggests the volunteers will only require a single dose of their vaccine in order to generate a targeted and potent immune response. If everything looks good as Phase 1 gets under way, then Phase 2 will launch before the end of the year. The team then hopes to continue the process with a Phase 3 clinical trial by the spring (2021).
Successful clinical trials represent enormous milestones in any vaccine development, but they are only part of the story. From the very beginning, Dr. Lewis and his team recognized the need to develop a vaccine against COVID-19 that is both biologically viable (safe and effective) and logistically feasible (to ship, store, and administer). The one often poses challenges for the other, but Dr. Lewis believes they have both sides covered.
“A good vaccine needs to be very stable to be shipped around the world,” he explains. “Some vaccines achieve this stability through freezing or refrigeration, but that can become difficult when the vaccine needs to reach and be usable in places that don’t have access to adequate freezing or refrigeration capacity. Our vaccine can be kept at room temperature for up to one month, however, so we are quite hopeful that it will be suitable for all parts of Canada and for low- and middle-income countries or remote regions everywhere.”
Manufacturing a successful vaccine, especially at the scale required to bring the worldwide pandemic under control, can also be complicated—but Dr. Lewis is undaunted.
“Our plan is to do everything,” he says simply. “Manufacturing for a DNA vaccine is very straightforward, so it can be ramped up quickly. We are working with the Alberta Cell Therapy Manufacturing (ACTM) facility here at the University of Alberta to make the doses for our clinical trials—and if everything is successful and approved for broader use, ACTM can produce one million doses per day. If needed, that capacity can actually be boosted to a maximum of four million doses per day.”
The team is working hard to create partnerships all over the world to support the development and potential distribution of the vaccine, but they also clearly take pride in working on a made-in-Canada solution to a global problem.
“We have a fantastic team of Canadian researchers spanning from the west coast to the east coast, and I feel very privileged to work alongside them,” says Dr. Lewis. “And if we get to protect Canadians in the end, that will be very gratifying.”
This article was reposted with permission from Canadian Institutes of Health Research. Visit cihr-irsc.gc.ca/ for more research on COVID-19.