Bite-sized vaccines and familiar faces

This week researchers at the University of Washington have published some encouraging data from a clinical trial they’ve been running using a live malaria vaccine that they’ve developed. Long term, they’ll make the vaccine in a test tube, but for now, while they work out its feasibility and effectiveness, they’re testing it by using mosquitoes themselves to vaccinate people! Sean Murphy…

Sean - The world needs a very highly effective malaria vaccine and, while a new vaccine was approved late last year, the efficacy of that vaccine is not as high as we would like. So one of the most successful ways to make vaccines is to take the organism that causes the disease and to weaken it and turn it into a vaccine. People have been trying to do that for malaria for actually decades and this study showed that this could be a very effective approach.

Chris - So how have you weakened it?

Sean - Well, the DNA of the malaria parasite has more than 5,000 genes. And, leading up to this study, some of the researchers involved figured out some genes that were really important for the parasite to survive in your liver. And if they made changes to the DNA, so that those genes no longer worked, they found that now the parasite couldn't make it through the liver stage. And therefore couldn't go on to cause like disease that we would see with a normal parasite.

Chris - How did you test this then? Because, obviously malaria is transmitted by mosquitoes normally, so how would you vaccinate a person?

Sean - So in this study, we actually use the mosquitoes as tiny little flying syringes because the form of the parasite that serves as the vaccine, we can only right now make it in mosquitoes. And what we know is that if people get about a thousand mosquito bites with these weakened parasites, they can end up being protected against the later 'challenge' with mosquitoes that carry the regular old malaria parasite.

Chris - How on earth do you persuade people to get a thousand mosquito bites?

Sean - Yeah. Well, first of all, it's not a thousand in one sitting, let me be clear about that. The bites were administered about 200 bites per sitting, and some people had some pretty intensely itchy arms after that. And so we pay a lot of attention to how to limit that. But, within a matter of a few days, usually that went away. But that was our strategy for vaccinating and the volunteers were really wonderful and generous of their time.

Chris - And what happened when these people got these hundreds of mosquito bites, did they mount a malaria response?

Sean - It's very clear that the people definitely mounted an immune response. We can see that people are making antibody responses against the parasite, but we also know that there are probably immune responses that we cannot measure when we just take blood from a vein. And that's why the challenge model is so important for us to actually be able to measure whether we succeeded or didn't with the vaccine.

Chris - And when you say challenge model, this is you coming along later and physically trying to infect people with malaria for real, to see if they're protected by the prior exposure to the weakened vaccine strain.

Sean - Yeah, that's correct. And we challenge them with usually five mosquito bites. We follow them for the emergence of the parasites in their blood, which would indicate that whatever we were trying to protect against in the liver did or did not work. So someone who had a good vaccine response wouldn't have the parasites emerging in their blood ever because they would be completely protected and we can follow that really closely.

Chris - And is that what you saw?

Sean - So what we saw in this study was that half of the vaccinated people were completely protected against infection. It's a very high bar to achieve complete protection against because even just one of the parasites that comes from the mosquito can go on to ignite the blood stage infection later on. So 99% reduction is not enough. You really have to achieve a hundred percent eradication of the parasite in your liver. What this study tells us is that this genetically attenuated parasite approach is actually quite promising. And the reason that we're not disappointed that we didn't get a hundred percent protection, is that we know that if we put the vaccine in by needle and syringe, it's likely to have a higher rate of protection. And that's because every time we give mosquito bites, the vaccine is to some extent stopped in its tracks right there in the skin. But if we give it by needle and syringe, it's likely that more of the vaccine will get to the liver. And if it gets to the liver, we think more of it will be able to do its purposeful role as a vaccine.

There has been a big stink in the media over the amount of untreated sewage being released along the UK coastlines, sometimes without anyone realising. Indeed, one report claims devices installed by water companies to monitor water quality failed to pick up a quarter of sewage dumps last year; in some cases, the equipment failed 90% of the time.

Perhaps as a result, following a bout of heavy rain, a pollution warning has gone out across 40 public beaches and swimming spots recently, and lead to renewed calls for action. Will Tingle spoke with Hugo Tagholm, Chief Executive and Co-founder of Surfers Against Sewage, about the potential implications these sewage dumps could have on public health…

Hugo - We're tracking thousands of sewage pollution events every year at beaches and at rivers. We know that last year alone water companies in England discharged over 2.6 million hours of sewage pollution, 370,000 separate events, at some of our best beaches and bathing waters. We tracked almost three and a half thousand sewage events and that's sort of between the red and yellow flags where people like to swim and expect never to come into contact with industrial pollution. So if we are now hearing that there aren't enough sensors and some of the sensors maybe faulty or broken, then perhaps what we are dealing with is just the tip of the iceberg for the problem for our beaches and for our coastline and maybe on a bigger scale for our rivers too. So we are really concerned. The water industry is presiding over a tidal wave of sewage, and it's simply not good enough.

Will - And is the reason behind the lack of this monitoring equipment simply because they aren't there or just that they're faulty?

Hugo - The industry now has an obligation to monitor and report on sewage discharges. Clearly, there's a process of installing and managing these sensors. It's these types of sensors that give us the data for the safer season river service, the real time data that we can give to the public to keep them safe and make sure they have the cleanest swimming experience at the beach. But the reasons behind the water industry not yet being fully up to speed with this are probably numerous. This is about the time it potentially takes to install them and manage them. And the investment it takes, but they have the money, they have the engineers and they have the resources. So we need to see them moving faster because that information is key to making the investments in the right places to end sewage pollution and protect our rivers and protect our coastline.

Will - We don't want any sort of water contamination, particularly in areas that we swim. So what kind of health problems could people be looking at if people are to swim in these waters?

Hugo - People shouldn't ever be exposed to sewage pollution. It could carry all sorts of pathogens that can make people ill, stomach infections, ear, eye, nose, throat infections. And it carries emerging threats like antibiotic resistant bacteria, which we've done studies on with the European Centre for the Environment and Human Health, which show that regular swimmers have three times the level of antibiotic resistant bacteria in their guts than the background population, even if it's diluted it still poses a big threat to human health. Dilution is not a solution. We really need to see the right solutions in place to protect both people and the environment from sewage pollution. Just 14% of our rivers meet good ecological status, our bathing water, sadly, languishes at the bottom of the European bathing water tables. We should be doing much better in aiming to have the best rivers in the world and also the best water quality in the world.

Will - And aside from holding our water and sewage companies accountable, is there anything else that we could be doing to improve the water quality of our UK coastlines and rivers?

Hugo - This is tightly linked to both the climate issue and the rewilding or the restoration of nature issue. We should be restoring nature, and there's a big movement to restore both terrestrial and marine ecosystems. There's CCGrass and oyster beds and kelp forests, on land forests, our rivers and natural habitats. And those land based ecosystems can take the pressure off water systems. They can slow down water, absorb the water in a more natural way and relieve that pressure on the sewer systems. Personally, people can also make sure they behave responsibly with water, you know, not wasting water, not flushing the wrong things down the loo, but this isn't an individual responsibility sort of issue. This is about an industry that is very profitable, can afford to build the infrastructure and invest in nature based solutions and make sure they're creating a system that's fit for the future, fit to face climate change, and fit both to supply water and protect nature at the same time.

Scientists estimate that about 80% of the genes we carry are involved in building the structure of our faces and hence the way we look. And so we’ve always suspected that, potentially, if you find someone who looks very like you, chances are you have a lot of the same genes in common. Now scientists have confirmed that’s the case, and it unlocks the possibility of predicting what someone might look like, based just on their genetic code. Julia Ravey spoke to Manel Esteller, from Josep Carreras Leukaemia Research Institute (IJC) in Barcelona, who’s been comparing people who aren’t related but nevertheless look very much alike…

Manel - We started with different levels of complexity in cells to know what is the main contributor to having similar faces; genetics, epigenetics - that is the regulation of DNA - and the microbiome - how many bacteria? What type of bacteria? It's difficult to give a number, but you can imagine that around 1000 to 2000 genes are relevant for the shape of our face.

Julia - And there are people out there who aren't twins. They're not even related as far as they know, but they look really, really similar. So why is this?

Manel - This is our study. Our study looked at these people that look very similar, but they're not related because we have gone back hundreds years, we have seen that these people that share very similar faces are not in any way related by family. And in this case, they share these genetic variants that relate to the shape and volume of our mouth nose, eyes, cheeks, but also to our height and weight.

Julia - Why do you think that there are these commonalities between people that aren't even related?

Manel - It's difficult to know why, but the most logical explanation for us is that this is happening by random chance. So there are now so many people in the world that they share these particular genetic sequences that relates to the shape of our face. Now we have more ways to find these people because internet and all the apps, the young generations and teens are now able to catch another person that looks like them.

Julia - Beyond the face, were there any other characteristics that these individuals had in common in terms of their genes?

Manel - There were other parts of the body that were related in this case. And also some other traits, like for example, the use of tobacco, the smoking, and to be right or left handed, they were shared. So this probably goes a little bit beyond the face.

Julia - And you sometimes see people in couples actually look very similar. Sometimes we're attracted to people who look like us. So is there any need to be worried if you're in a relationship with someone who looks a bit like you in terms of potentially having some recessive traits that might come together in offspring to produce something which isn't overly great?

Manel - In theory, from a genetic point of view, it's better that you mix up with somebody that is different. In fact, some people that live together, they start looking similar and because they live in the same environment, you know, the same contamination or the same job, they eat the same things. So it's possible that recent conversions later in humans, these things are not inherited, they are acquired. They relate a lot of them to epigenetic changes, the content of the microbiome, and these are things that relates to our lifestyle.

Julia - So if I find someone who looks like me say on the other side of the world, I shouldn't be worried that I've got a long lost twin?

Manel - If it's perfectly identical, you can worry, but being perfectly identical, it's very difficult. So they look alike, but they're not, of course, perfectly identical. You can only be a copycat if you share 100% of your genome.

Julia - What are the consequences of this work?

Manel - Maybe now from DNA, we can think of constructing a face and this can be important in forensic medicine, for example, to find somebody responsible of a crime, just from the DNA, to be able to draw a face. So maybe now there are some data you can start doing that.