Mark Kendall
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It's a pleasure to be here in Edinburgh, Scotland, the birthplace of the needle and syringe. Less than a mile from here in this direction, in 1853 a Scotsman filed his very first patent on the needle and syringe. His name was Alexander Wood, and it was at the Royal College of Physicians. This is the patent. What blows my mind when I look at it even today is that it looks almost identical to the needle in use today. Yet, it's 160 years old.

So we turn to the field of vaccines. Most vaccines are delivered with the needle and syringe, this 160-year-old technology. And credit where it's due — on many levels, vaccines are a successful technology. After clean water and sanitation, vaccines are the one technology that has increased our life span the most. That's a pretty hard act to beat.

But just like any other technology, vaccines have their shortcomings, and the needle and syringe is a key part within that narrative — this old technology. So let's start with the obvious: Many of us don't like the needle and syringe. I share that view. However, 20 percent of the population have a thing called needle phobia. That's more than disliking the needle; that is actively avoiding being vaccinated because of needle phobia. And that's problematic in terms of the rollout of vaccines.

Now, related to this is another key issue, which is needlestick injuries. And the WHO has figures that suggest about 1.3 million deaths per year take place due to cross-contamination with needlestick injuries. These are early deaths that take place.

Now, these are two things that you probably may have heard of, but there are two other shortcomings of the needle and syringe you may not have heard about. One is it could be holding back the next generation of vaccines in terms of their immune responses. And the second is that it could be responsible for the problem of the cold chain that I'll tell you about as well.

I'm going to tell you about some work that my team and I are doing in Australia at the University of Queensland on a technology designed to tackle those four problems. And that technology is called the Nanopatch. Now, this is a specimen of the Nanopatch. To the naked eye it just looks like a square smaller than a postage stamp, but under a microscope what you see are thousands of tiny projections that are invisible to the human eye. And there's about 4,000 projections on this particular square compared to the needle. And I've designed those projections to serve a key role, which is to work with the skin's immune system. So that's a very important function tied in with the Nanopatch.

Now we make the Nanopatch with a technique called deep reactive ion etching. And this particular technique is one that's been borrowed from the semiconductor industry, and therefore is low cost and can be rolled out in large numbers.

Now we dry-coat vaccines to the projections of the Nanopatch and apply it to the skin. Now, the simplest form of application is using our finger, but our finger has some limitations, so we've devised an applicator. And it's a very simple device — you could call it a sophisticated finger. It's a spring-operated device. What we do is when we apply the Nanopatch to the skin as so — (Click) — immediately a few things happen. So firstly, the projections on the Nanopatch breach through the tough outer layer and the vaccine is very quickly released — within less than a minute, in fact. Then we can take the Nanopatch off and discard it. And indeed we can make a reuse of the applicator itself.

So that gives you an idea of the Nanopatch, and immediately you can see some key advantages. We've talked about it being needle-free — these are projections that you can't even see — and, of course, we get around the needle phobia issue as well.

Now, if we take a step back and think about these other two really important advantages: One is improved immune responses through delivery, and the second is getting rid of the cold chain.

So let's start with the first one, this immunogenicity idea. It takes a little while to get our heads around, but I'll try to explain it in simple terms. So I'll take a step back and explain to you how vaccines work in a simple way. So vaccines work by introducing into our body a thing called an antigen which is a safe form of a germ. Now that safe germ, that antigen, tricks our body into mounting an immune response, learning and remembering how to deal with intruders. When the real intruder comes along the body quickly mounts an immune response to deal with that vaccine and neutralizes the infection. So it does that well.

Now, the way it's done today with the needle and syringe, most vaccines are delivered that way — with this old technology and the needle. But it could be argued that the needle is holding back our immune responses; it's missing our immune sweet spot in the skin. To describe this idea, we need to take a journey through the skin, starting with one of those projections and applying the Nanopatch to the skin. And we see this kind of data. Now, this is real data — that thing that we can see there is one projection from the Nanopatch that's been applied to the skin and those colors are different layers. Now, to give you an idea of scale, if the needle was shown here, it would be too big. It would be 10 times bigger than the size of that screen, going 10 times deeper as well. It's off the grid entirely. You can see immediately that we have those projections in the skin. That red layer is a tough outer layer of dead skin, but the brown layer and the magenta layer are jammed full of immune cells. As one example, in the brown layer there's a certain type of cell called a Langerhans cell — every square millimeter of our body is jammed full of those Langerhans cells, those immune cells, and there's others shown as well that we haven't stained in this image. But you can immediately see that the Nanopatch achieves that penetration indeed. We target thousands upon thousands of these particular cells just residing within a hair's width of the surface of the skin.

Now, as the guy that's invented this thing and designed it to do that, I found that exciting. But so what? So what if you've targeted cells? In the world of vaccines, what does that mean? The world of vaccines is getting better. It's getting more systematic. However, you still don't really know if a vaccine is going to work until you roll your sleeves up and vaccinate and wait. It's a gambler's game even today.

So, we had to do that gamble. We obtained an influenza vaccine, we applied it to our Nanopatches and we applied the Nanopatches to the skin, and we waited — and this is in the live animal. We waited a month, and this is what we found out. This is a data slide showing the immune responses that we've generated with a Nanopatch compared to the needle and syringe into muscle. So on the horizontal axis we have the dose shown in nanograms. On the vertical axis we have the immune response generated, and that dashed line indicates the protection threshold. If we're above that line it's considered protective; if we're below that line it's not. So the red line is mostly below that curve and indeed there's only one point that is achieved with the needle that's protective, and that's with a high dose of 6,000 nanograms. But notice immediately the distinctly different curve that we achieve with the blue line. That's what's achieved with the Nanopatch; the delivered dose of the Nanopatch is a completely different immunogenicity curve. That's a real fresh opportunity. Suddenly we have a brand new lever in the world of vaccines. We can push it one way, where we can take a vaccine that works but is too expensive and can get protection with a hundredth of the dose compared to the needle. That can take a vaccine that's suddenly 10 dollars down to 10 cents, and that's particularly important within the developing world.

But there's another angle to this as well — you can take vaccines that currently don't work and get them over that line and get them protective. And certainly in the world of vaccines that can be important. Let's consider the big three: HIV, malaria, tuberculosis. They're responsible for about 7 million deaths per year, and there is no adequate vaccination method for any of those. So potentially, with this new lever that we have with the Nanopatch, we can help make that happen. We can push that lever to help get those candidate vaccines over the line. Now, of course, we've worked within my lab with many other vaccines that have attained similar responses and similar curves to this, what we've achieved with influenza.

I'd like to now switch to talk about another key shortcoming of today's vaccines, and that is the need to maintain the cold chain. As the name suggests — the cold chain — it's the requirements of keeping a vaccine right from production all the way through to when the vaccine is applied, to keep it refrigerated. Now, that presents some logistical challenges but we have ways to do it. This is a slightly extreme case in point but it helps illustrate the logistical challenges, in particular in resource-poor settings, of what's required to get vaccines refrigerated and maintain the cold chain. If the vaccine is too warm the vaccine breaks down, but interestingly it can be too cold and the vaccine can break down as well.

Now, the stakes are very high. The WHO estimates that within Africa, up to half the vaccines used there are considered to not be working properly because at some point the cold chain has fallen over. So it's a big problem, and it's tied in with the needle and syringe because it's a liquid form vaccine, and when it's liquid it needs the refrigeration.

A key attribute of our Nanopatch is that the vaccine is dry, and when it's dry it doesn't need refrigeration. Within my lab we've shown that we can keep the vaccine stored at 23 degrees Celsius for more than a year without any loss in activity at all. That's an important improvement. (Applause) We're delighted about it as well. And the thing about it is that we have well and truly proven the Nanopatch within the laboratory setting. And as a scientist, I love that and I love science. However, as an engineer, as a biomedical engineer and also as a human being, I'm not going to be satisfied until we've rolled this thing out, taken it out of the lab and got it to people in large numbers and particularly the people that need it the most.

So we've commenced this particular journey, and we've commenced this journey in an unusual way. We've started with Papua New Guinea.

Now, Papua New Guinea is an example of a developing world country. It's about the same size as France, but it suffers from many of the key barriers existing within the world of today's vaccines. There's the logistics: Within this country there are only 800 refrigerators to keep vaccines chilled. Many of them are old, like this one in Port Moresby, many of them are breaking down and many are not in the Highlands where they are required. That's a challenge. But also, Papua New Guinea has the world's highest incidence of HPV, human papillomavirus, the cervical cancer [risk factor]. Yet, that vaccine is not available in large numbers because it's too expensive. So for those two reasons, with the attributes of the Nanopatch, we've got into the field and worked with the Nanopatch, and taken it to Papua New Guinea and we'll be following that up shortly.

Now, doing this kind of work is not easy. It's challenging, but there's nothing else in the world I'd rather be doing. And as we look ahead I'd like to share with you a thought: It's the thought of a future where the 17 million deaths per year that we currently have due to infectious disease is a historical footnote. And it's a historical footnote that has been achieved by improved, radically improved vaccines. Now standing here today in front of you at the birthplace of the needle and syringe, a device that's 160 years old, I'm presenting to you an alternative approach that could really help make that happen — and it's the Nanopatch with its attributes of being needle-free, pain-free, the ability for removing the cold chain and improving the immunogenicity. Thank you. (Applause)