 If I told you to imagine what the world will look like in 10 years time, would you picture a world where a small cut or a sore throat could kill? A world where 10 million people will die every year from diseases which we can currently treat, because that is the reality we face due to antibiotic resistance. In just 10 years time all the antibiotics we have will be completely ineffective, meaning research into new antibiotics is crucial. But despite our best efforts, in the past 30 years we've only discovered one new antibiotic, meaning research into alternatives to antibiotics, such as vaccines, is equally as crucial in combating this bacterial apocalypse. And that's what I will be talking to you about today. My name's Kellem, and I'm doing my masters up at the Faculty of Health, Medical and Health Sciences in the Infection and Immunity Lab under the supervision of Associate Professor Thomas Profft and Dr Jaycelyn Lowe. And this is my project, Pill Vax, a novel vaccine against pneumococcus. Now you probably haven't heard of pneumococcus, but you probably have heard of the three nasty infections which it can cause, pneumonia, infection of the lungs, meningitis, infection of the brain, and infections of the bloodstream. Together these infections kill more than 1.5 million children every year, making pneumococcus the number one cause of child mortality. More than 95% of these deaths occur in the developing world, where a lack of resources makes it extremely difficult to treat these infections. But what's more alarming is more than 40% of these infections are resistant to antibiotics, making them untreatable, and emphasising the urgent need for an effective vaccine against pneumococcus, because the only way to deal with these infections which you can't treat is to prevent them happening in the first place. The reason I say effective vaccine is because we in fact already have two vaccines against pneumococcus. Pneumovax and Privna, but as evidenced by the still alarmingly high mortality rates, these vaccines are ineffectual, and that's because of the way they are designed. So a vaccine is made up of two components, the target or antigen and the danger signal or the adjuvant. So the antigen tells the immune system what to look for, so the next time it encounters that antigen it knows to make a response. And the adjuvant tells the body that that antigen is dangerous and it's something that it should respond to. And it's because of a poor choice of both antigen and adjuvant that our current vaccines fail to lessen the burden of pneumococcus on our society. So first of all the antigen, the antigen that these vaccines use is capsular polysaccharide, which is a sticky coating on the outside of the bacteria, kind of like the bacteria's clothes. But just like we're all wearing different clothes today, each strain of pneumococcus has a different capsule. Now there are over 94 different strains of pneumococcus, and therefore 94 different capsules. And currently the largest vaccine only covers 30 of these capsules, meaning even vaccinated individuals are vulnerable to a huge proportion of pneumococcal disease. In fact, vaccinated individuals have been shown to be more susceptible to infection with the non-vaccine strains, demonstrating how ineffective our vaccines are. Now to the adjuvant. The adjuvant they use is an inactivated bacterial toxin, which creates a strong immune response, but is expensive to produce and couple to the polysaccharide, making it financially inaccessible to the third world where it is most desperately needed. One vaccine dose costs $136, which is more than half the annual income of entire African family, demonstrating just how impossible it is for these families to afford this vaccine. The adjuvant also needs to be constantly refrigerated, meaning some families have to travel thousands of miles just to receive the dose of this vaccine in third world countries where refrigeration is not readily available. They have to make this journey because they are desperate. These diseases kill one of their children every 20 seconds, and we need to do better for these families. And that's where my research comes in. By changing both the antigen and the adjuvant, my research aims to overcome the shortfalls of our current vaccine and develop the vaccine, which can give these families hope. So how are we going to do this? First of all, the antigen. Instead of using that capsular polysaccharide, I'm using a protein called PSPA, which as you can see is present in all strains of pneumococcus and is highly conserved. If we go back to that clothing analogy, it's kind of like the tag. No matter what you're wearing, all clothes have a tag. And my vaccine will protect against all pneumococcal disease because I use this PSPA. Now if we go to the adjuvant, this is where the real science comes in. My supervisor has devised a revolutionary vaccine technology which has inbuilt adjuvency and is cheap and easy to mass produce, making it ideal for use in the third world. It's called Pilvax and this is how it works. So just like humans are covered in hair, bacteria are also covered in hair. But unlike in humans, their hair is not just for decoration. It acts kind of like velcro to help the bacteria stick to human cells and invade the body. So the hairs are called pilae and just like human hair is made of keratin, they are made up of this protein called Spire 128. Now Pilvax works by combining your antigen of interest with that Spire 128 protein to create pilae, which express lots of that antigen. This is a highly stable structure and because the surface is covered in these pilae, the antigen is highly amplified and generates a strong immune response. And the bacteria itself acts as the adjuvant to signal that the antigen is dangerous. But we use a special bacteria called Lactococcus, which is actually the bacteria found in yogurt and cheese and so it doesn't cause you any harm and the vaccine is totally safe. Now to demonstrate how powerful this vaccine is, this vaccine technology I've got a graph here of our pilot study. On the y-axis I've got the antibody titer, which is just a measure of the immune response. And along the x-axis I've got the three vaccines. So if you vaccinate with that antigen alone, you get no response because you need that adjuvant to generate an immune response. If you add a conventional adjuvant, you get a response. But if you vaccinate with pilvax, you get a response that is three logs higher, which is 1,000 times as potent, demonstrating just how powerful delivering antigens in this way is. But not only is it powerful and totally safe, it's cheap and easy to mass produce. And that's because we use live bacteria. Now live bacteria can be frozen down into this powder, which can be easily shipped and distributed. It doesn't need refrigeration. It's lightweight. It's cheap. And you can get it to those third world countries where it's most needed. You just add water and the vaccine is ready to go. And what's even better is the vaccine does not require any needles. It's delivered as a nasal spray. So you can just spritz it up your nose and you're good to go. We've also tested delivering it orally and it works just as effectively so in the future it could be used through an ice cream or a yogurt. Now don't tell me that's not revolutionary. So where am I up to? Well there's two steps to this project, making the vaccine and testing the vaccine. So when you're making the vaccine you are genetically modifying that polys and that makes it harder for the bacteria to express. So to determine whether your vaccine is going to be effective you have to measure the amount of bacterial hair on the surface. So we do that using fluorescence. So I've got a graph here on the y-axis I've got fluorescence which is just a measure of that bacterial hair. And along the bottom I've got my four vaccine strains that I've made. And as you can see Strain 1 and Strain 3 both express quite high amounts of hair so I haven't been able to get it to go any higher. So now I'm testing those strains in mice to measure their immune response. So for the last two months I've been vaccinating mice. You give them three doses every fortnight and next week I will be measuring their immune response so I'm very excited. It's been a long time coming to this and it's very exciting so watch this space. But I'm not working alone. You heard a presentation from one of my lab members earlier tonight and we're also working on vaccines against influenza, group A streptococcus infections like Jeremy was talking about and staff infections so we've got a lot of vaccines on the go and I'm very privileged to be working in a lab where we're working at the forefront of our field. So I just like to thank all my lab members for their contributions to my research. I'd like to thank the University for funding this research because without their funding we couldn't do this groundbreaking research and I'd like to thank Exposure for giving me the opportunity to share it all with you tonight.