Do you know where and when the first needles and syringes appeared? In 1853, at the Royal College of Physicians, a few kilometers from Edinburgh, the Scotsman Alexander Wood registered his very first patent for a needle and syringe. Here is the patented design. The most surprising thing is that it looks almost identical to the needle we use today.
Let's turn to the field of vaccines. Most of them are administered with a needle and syringe — this technology is 160 years old. To her credit, in many ways, vaccines — successful technology. After clean water and sanitation, vaccination — the technology that increased life expectancy the most. This is a fact that is quite difficult to overcome.
But just like any other technology, vaccines have their drawbacks, and the needle and syringe — the key point of this story, this old technology. Let's start with the obvious: many of us don't like needles and syringes. Moreover, 20% of the population has something called trypanophobia, — fear of injections. This is more than just a dislike, it is an active avoidance of vaccinations due to a fear of injections. Which is problematic due to the massive use of vaccines.
The second key issue — injuries resulting from the use of needles. According to WHO statistics, 1.3 million deaths per year result from the subsequent infection of vaccine injection sites.
But besides these two well-known shortcomings, there are two more that you have hardly heard of. First, they are believed to delay the development of the next generation of vaccines in terms of the immune system's response to them. Second, they can cause a cold chain problem, which we will discuss next.
Dr Makr Kendal shared what he and his team are working on at the University of Queensland in Australia. It's a technology called Nanopatch that addresses these four problems:
— Here is a Nanopatch sample. With the naked eye, we see only a square smaller than a postage stamp, but under a microscope, we see thousands of tiny protrusions invisible to the human eye. There are about 4,000 of them in this particular square. I have designed these projections to play the key role — work with the immune system of the skin. This is a very important feature built into Nanopatch.
We create Nanopatch with a method called deep reactive ion etching. This method was adopted from the semiconductor industry, hence it is low cost and can be used to produce a huge amount of material.
We use vaccines as a dry coating of Nanopatch protrusions that are applied to the skin. The simplest example of using — on the finger. However, fingers are not always comfortable, which is why we invented the applicator. This is a very simple device, you can call it a "smart finger". The device is spring operated. We came up with the following: when applying Nanopatch to the skin — (Click) — several things happen at once. First, the "Nanopatch" protrusions pass through the dense outer layer, and the vaccine is released very quickly — in fact, less than a minute. The Nanopatch can then be removed and discarded. And, of course, you can reuse the applicator itself.
Now you have an idea of what Nanopatch is and its key benefits are immediately clear. We talked about how it does not involve the use of a needle, — you can't even see these protrusions. This is how we solve the problem of trypanophobia.
Let's step back a bit and think about the other two really important benefits: the first — improved immune responses due to route of administration, second — getting rid of the cold chain.
Let's start with the first one, with the idea of immunogenicity. It will take a little time to understand it, but I will try to explain in simple terms. Let's digress a bit and understand how vaccines work. Their action is to introduce an antigen into the body, which is a safe form of bacteria. This bacterium, as it were, deceives the body, forcing it to develop an immune response, learning and remembering how to deal with "intruders". When the real "intruder" appears, the body will immediately react in a learned way and neutralize the infection.
Today, all this is done through a needle and syringe. Most vaccines are administered this way — by this old technology. But there is an opinion that the needle delays the immune response; it misses the "sweet spot" on the skin. To make this point clear, we will have to go on a skin journey by taking one of these protrusions and applying the Nanopatch to the skin. We will see data like this. This is real data. This little thing — one of the Nanopatch protrusions applied to the skin, and these colors — different layers. To represent scale: if the needle were shown here, it would be too large. 10 times the size of this screen and penetrates 10 times deeper too. She is completely off the grid. You immediately see these protrusions that have entered the skin. This red layer — a dense outer layer of dead skin, and the brown and purple layers are densely packed with immune cells. As an example, in the brown layer there is a particular type of cell called Langerhans cells. Every square millimeter of our body is filled with Langerhans cells — immune cells. But there are others that we have not included in this picture. You can see that the Nanopatch goes really deep into the skin. The target is the thousands upon thousands of these cells within the hair-thin layer on the surface of the skin.
which we have not placed in this picture. You can see that the Nanopatch goes really deep into the skin. The target is the thousands upon thousands of these cells within the hair-thin layer on the surface of the skin. which we have not placed in this picture. You can see that the Nanopatch goes really deep into the skin. The target is the thousands upon thousands of these cells within the hair-thin layer on the surface of the skin.
As the person who invented and patented Nanopatch, I find this very inspiring. Well, so what? So what if we target these cells? What does this mean in the world of vaccines? The world of vaccines is getting better, more systematic. However, it's still hard to know for sure if a vaccine will work until you roll up your sleeves, give the shot, and wait. Even today it is a game of roulette.
When developing the methodology, we also had to play with it. We took the flu vaccine, applied it to the Nanopatch, applied the Nanopatch to the skin, and waited for the — And all this on a live animal. We waited a month and this is what we found. This is a slide showing the immune responses we elicited with Nanopatch compared to the injection that elicited them in the muscle. The horizontal axis shows the dose in nanograms. On the vertical axis — generated immune response. But this dotted line indicates a protective threshold. If we are above this line, the reaction is supposed to be defensive; if below — then no. The red line is mostly below this curve, and in fact there is only one point obtained with a needle in the protection zone, and this is at a high dose of 6,000 nanograms. But notice this completely different curve, which we see as this blue line. These are the results of Nanopatch. Injected Nanopatch dose — it's a completely different immunogenic curve. A very encouraging opportunity. All of a sudden, we have the newest leverage in the world of vaccines. We can use it like this: take an effective but too expensive vaccine and get protection using a hundredth of the dose needed with a needle. So the cost of a 10 dollar vaccine is reduced to 10 cents, which is incredibly important in the developing world.
required for needle insertion. So the cost of a 10 dollar vaccine is reduced to 10 cents, which is incredibly important in the developing world. required for needle insertion. So the cost of a 10 dollar vaccine is reduced to 10 cents, which is incredibly important in the developing world.
Now I would like to turn the conversation to another key drawback of today's vaccines — the need for cold chain management. As the name suggests, "cold chain" — it is the need to keep vaccines refrigerated immediately after production and all the way to use. This causes some logistical difficulties, but there are ways to achieve this. This is a somewhat critical case, but it helps to illustrate the logistical challenges in specific resource-poor environments, how difficult it can be to deliver vaccine chilled and maintain a cold chain in such environments. If the vaccine is too warm, it might not work, but it's interesting that if it's too cold, then it might not work either.
The stakes are high. According to WHO, in Africa, the effectiveness of about half of the vaccines used is reduced to zero due to the fact that at some point the "cold chain" was broken. This is a big problem with the needle and syringe. The syringe uses a liquid vaccine that needs constant refrigeration.
A key feature of Nanopatch — dry vaccine. When it is in this state, cooling is not required. In my laboratory, we have demonstrated that we can keep the vaccine stored at +23°C for more than a year without losing its effectiveness. This is a very important improvement. And what is important, with this we finally and irrevocably proved the work of Nanopatch in the laboratory. As a scientist, I really like it, I love science. However, as an engineer, as a biomedical engineer, and also as a person, I will not be satisfied until we take the "Nanopatch" out of the lab and provide it to a huge number of people around the world, especially those who need it most.
We started this journey in a rather unusual manner. We started from Papua — New Guinea.
State of Papua — New Guinea — example of a developing world country. It is about the same size as France, but it suffers from many of the key shortcomings of the vaccine world today. Here are the logistics: there are only about 800 refrigerators in the country to keep vaccines chilled. Many of them are old, like this one in Port Moresby, many are broken, and most are not in the mountains, where they are most needed. This is problem. In addition, in Papua — New Guinea has the world's largest percentage of HPV cases — human papillomavirus that can cause cervical cancer. Yet these vaccines are not available in large quantities because they are too expensive. For these two reasons, taking into account the peculiarities of Nanopatch, we took root in this area and worked with Nanopatch, brought it to Papua —
It's not easy to do this kind of work. This requires a lot of energy and effort. But there is no better job for me. Thinking about the future, I would like to share with you a thought: imagine a future without 17 million deaths a year due to infectious diseases — this is a historical fact achieved by improved, radically improved vaccines. Standing here today in front of you practically at the birthplace of the needle and syringe, — device, which is already 160 years old, — I present to you an alternative approach that can really give us such a future. "Nanopatch" does not require the use of a needle, does not cause pain, eradicates the "cold chain" and improves immunogenicity.
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