Deborah Fuller, PhD, Professor in the Department of Microbiology at University of Washington School of Medicine talks about a potential universal flu vaccine.
Interview conducted by Ivanhoe Broadcast News in July 2018.
Tell me: we know Dr. Baker is the front end guy, but what happens after he develops the proteins that potentially could lead to the universal flu vaccine?
Dr. Fuller: David and I were actually separately working on concepts for a universal flu vaccine. His is in the design of a novel immunogen to present different sequences from influenza that would force the body to induce responses that would protect you against any strain of influenza. We were separately working on identifying what those sequences might be from the flu viruses and also developing a delivery technology, a way of actually administering the vaccine to induce these responses most effectively. We got together and began to discuss our technologies and we realized we could combine them together, that they would be much better together than they would be independently. Both work separately, but in combination are going to be even more effective. What we ended up doing is we discussed how we were going to combine this. What David has developed is a novel computation designed protein platform. There he can present immunogens in a unique way that harnesses the immune system to be much more potent than what would be with, say, your typical vaccines or antigens that go in vaccines. We had identified sequences from influenza virus that, if targeted by the immune system, were going to be able to provide you protection against any strain of influenza that comes around. The problem is that those sequences that we identified were very poorly immunogenic. If you combine them, though, with the nanoparticle based protein platform that David Baker’s group is developing, you get much greater immunogenicity. That by itself is just sort of the vaccine concept. Then how do you actually deliver that? For many years my lab has been working on the concept called DNA vaccines and this is a different way of vaccinating than your typical vaccines. Most vaccines like, for example, your current flu vaccine is just the virus that is inactivated and injected into you. Other types of vaccines are like; a part of the virus is isolated and then grown up in a dish, and then injected into you. That’s like your hepatitis B vaccine. Still, there are other types of viruses that we call live attenuated viruses. These are weakened viruses that replicate maybe a couple of times in your body and then they poop out, then you actually get an immune response. That’s like your measles vaccine. DNA vaccines are none of the above, but they’re most similar to your hepatitis B vaccine in the sense that we’re only going to encode a small portion of the virus, not the entire virus. Generally, you produce this protein from the vaccine in a dish, and you inject that into the body. Instead, what we do is we inject the genetic material, the genetic code for that antigen directly into your own cells of your skin, so your own body actually is producing that particular vaccine. The big advantage of that is that you can actually develop a vaccine extremely quickly. You only need the genetic sequence of whatever virus happens to be floating around. In the case of flu, that is a huge advantage because every year flu season comes by, the flu virus emerges and the pandemic might emerge and we have to act quickly to block that virus to induce immunity in the population so they’re resistant to the infection. If influenza virus were to emerge, it would take nine months from the time that they identified the virus to the time that you’d actually be able to inject that into people. By then you have a pandemic. Most mortality and morbidity that occurs with flu occurs in the first three to six months. If you take nine months to produce a vaccine it’s too little, too late. DNA vaccine takes less than three months to produce, so by the time you’ve identified the genetic sequence, you can get that into people in three months.
And that would protect you against all types of flu?
Dr. Fuller: Correct. That’s where our collaboration with David Baker is very important. In our earlier studies with DNA vaccines for influenza, we would identify the sequences from influenza viruses. These are sequences that all influenza viruses share, so if we can do some immune response against them, we’re going to protect against any strain of influenza. When we injected that, and we did a human clinical trial, we found that the immune responses were not very strong because we were only producing very small amounts of the protein in the body. The way the collaboration with David Baker works is that if we can actually make the body see these immunogens better, then we can actually jack up the immune response.
And that’s what he’s doing.
Dr. Fuller: And that’s what he’s doing. His group is designing this sort of nanoparticle-based type of immunogen that’s going to present these sequences in a unique way that makes the body respond even more strongly to it. By combining our two technologies, we’re going to have the advantages of this rapid development of a vaccine: pain free delivery into the skin with no needle and a very immunogenic antigen that stimulates strong responses.
And the delivery was problematic, wasn’t it? And then tell us about the birth of the gene gun.
Dr. Fuller: Yeah. So, the birth of the gene gun came about alongside the birth of DNA vaccine. DNA vaccines are just genetic material injected into the body and then you produce your own vaccine. The first DNA vaccines were actually delivered just with the needle and syringe into your muscle, but that was very inefficient. Very little DNA got into the cells and very small amounts of protein were produced. These were the very first clinical trials. When they took those and tested them in people, they found they got no immune response whatsoever with a needle and syringe injected DNA vaccine, so we developed the gene gun. The idea of the gene was to try to circumvent the issue. The main problem with the needle and syringe is poor uptake of the DNA into your own cells and the gene gun bypasses that by delivering the DNA directly into the cells of the skin. What we do is we came up with a sort of nanoparticle injection in which we put the DNA and code it on small, one micron sized gold particles. Those gold particles are accelerated by a gene gun at high velocity and then transferred into the cells of the skin. It’s completely pain free. The particles are so small that you don’t actually feel them. It’s sort of like multiple little micro-injections where one particle goes into one cell. That results in a much more efficient delivery of the DNA. More of your cells are receiving the DNA; more of your cells are producing the vaccine. So, we got much better immune responses and positive results in the first human clinical trials with the gene gun.
So if it is not being injected, is it just being sucked into your skin from osmosis or how is it getting in?
Dr. Fuller: Yeah. With the gene gun, it’s actually being shot in like a bullet, directly into the cells.
But it doesn’t hurt?
Dr. Fuller: No, it doesn’t hurt at all because they’re just much too small. They penetrate only the very top layers of your skin, so it never gets into the lower layers where you can have nerves and things that you actually feel. In clinical trials, people said it felt like a puff of air. On a scale of one to five, where five is needle stick, they said it felt like a one.
So you’ve already started animal testing right?
Dr. Fuller: Yeah, yeah.
How is that coming?
Dr. Fuller: Right. What we’re doing now in my lab here at the University of Washington is we’re working on developing an even better gene gun, one that actually is going to be able to deliver more DNA into more cells and actually achieve that with fewer and lower doses. We’re now working on re-engineering the device, a new clinical gene gun, and we’re testing that currently in both mice as well as non-human primates.
So the gene gun testing is different than the universal flu vaccine development?
Dr. Fuller: Yeah.
So simultaneously, neither one of them is ready to go yet?
Dr. Fuller: Correct, yeah. The gene gun, it’s like a platform technology, right? It can deliver a universal flu vaccine, but if you think about it, it could deliver DNA for almost any type of virus. So we could make other types of vaccines with the gene gun. That’s similar really for David Baker’s immunogen design platform; it’s the same way where he can design what I think is more of a scaffold. The scaffold to prevent viral immunogens, or sequence where he could actually present flu or HIV or anything could actually be presented on this scaffold. So, we’re developing separate technologies, but we’re going to combine them together to make a much more effective strategy to induce responses.
So, now about flu, specifically timeframe: when might we be seeing human clinical trials? When might the mom with the two kids be able to immunize themselves with universal flu vaccine?
Dr. Fuller: It takes a while to actually develop a vaccine from the start of the bench here in the lab, all the way to clinical trials, and then all the way into the population so they can go to the pharmacy and have that administered. We’re looking at least five to ten years before you see the first universal flu vaccine from our group actually emerge to be available for the public, but I would say within less than five years we could begin the first Phase I clinical trials.
What haven’t I asked you that you think should be included in the story, if anything?
Dr. Fuller: In terms of influenza or the technology?
Either, anything.
Dr. Fuller: I think I would just add that when DNA vaccines first came out, everybody thought it was going to be the next best thing. All vaccines would eventually get replaced. But the field hit a major bump in the road in terms of DNA vaccines and that was when they first injected them with the needle and syringe. They were poorly immunogenic in humans, and they didn’t work at all in clinical trials. But there is now resurgence in interest in DNA vaccines. There are a lot of new technologies including the gene gun, as well as novel immunogens like David is designing. Or adjuvants and the like that other groups we’re collaborating with are developing. I believe DNA vaccines are back on the rise, and they will be the new future of vaccines going forward. If you think about it, all you need is plasma DNA and you can actually develop a vaccine in less than three months. It’s going to be, I think at least, initially part of the answer for new emerging pandemics or things that we don’t know might be coming down our way in terms of pathogens. DNA vaccines are going to provide a real exciting way to address that.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Bobbi Nodell
206-543-7129
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
