 Blutang virus is transmitted to its ruminant host almost entirely by biting midges, which we call colicoides. So this means it's a non contagious disease. So if you have an infected sheep, which shows clinical signs of Blutang, the sheep next to it will not be infected by the virus directly by passing on from one sheep to the other. The virus can only transmit if the biological vector colicoid is biting midges is around. So the virus then replicates in the insect and eventually after a certain time period it will reach the salivary gland. And once it has reached the salivary gland the next time this now infected midge feeds on a non-infected suitable mammalian host. So in the case of Blutang again ruminants, sheep, cattle, it can then transmit the virus during that blood meal back into the mammalian host and then the virus starts its replication cycle in this host again. And this is a really intriguing relationship because it doesn't function as a mere needle transmission at all. There's more and more research for example that the saliva has a very active role potentially in pathogen transmission because these insects have to salivate to stop blood coagulation and immune responses because if so their saliva is pharmaceutical active it contains anticoagulants because if they otherwise would try to feed the blood would immediately clot and then you can't take it up. But by having these bioactive molecules in their saliva they can prevent this blood clotting and they are able to take up a blood meal. Because it is a non-contagious transmission classical methods we use like preventing contact, restricting animal movement although they are still necessary they have a far less impact on a vector-borne disease. Animal movements are important to not dislocate the virus throughout an entire country so of course if you moved an animal from southern England to northern England you could almost create a second outbreak. However on a local scale once the local insect population is infected they will fly. They will not stop. You can't restrict them. You can't say excuse me you are now a movement restriction. So even if you don't if you do have animal movement controls the moment that virus is in the local insect population you have lost it because it will still be able to be transmitted those insects will still fly and infect neighboring farms. So this is one of the challenges of dealing with a vector-borne transmitted pathogen and this is why if you are a free country and you're fearing the incursion of a vector-borne disease it is so important to catch it early because what you are trying to do is find it and remove those animals or at least get them out of being exposed to so many biting insects before the local insect population is completely infected. The Puerbrat Institute has an in-sectory where we breed several insect species so mosquitoes and sub-biting flies, moxes, citrons and also colicoid is biting witches. In our Blutang research which is mainly Blutang pathogenesis research or transmission research or immune response and vaccine research we do the vast majority of our work with those mammalian hosts which are really in nature infected and affected by this virus. So we use sheep, goat and cattle because if you carry out research in something as complex as pathogenesis so where is this virus going and how is it causing disease or something like the immune response which is very species-specific we feel that it is an incredibly advantage to actually be able to use the host which is affected by this disease. We would obtain our study animals like sheep or goats or cattle from a commercial farm these are normal farm animals and that the moment they come into our isolation units they are incredibly monitored. So depending on which type of study we do we would treat them we would give them painkillers. So one question which is often raised when we talk about our work and describe our work is could we do our research without using animals. So we do a lot of work with primary cell cultures where we just get blood or samples from animals which which are put down anyway to establish primary cells to establish organ cultures and we carry out infection studies of these cells we even we have a project where we also assess the response of these cells to insect saliva to already get an idea what is going on what kind of cytokines are being made how do they respond is a difference when the virus is on these cells we send without Mitch saliva so we have developed a method to collect Mitch saliva by making them making them spit into a filter and we can wash off the saliva so we have a really active project to get our research to a level as far as we can by not using animals but there's only so far as we can go. When it comes to big questions like transmission. When it comes to big question like is this vaccine safe is this vaccine efficient how does the animal respond up on challenge we cannot carry out this work without the use of life and animals. The vertebrate immune system is way too complex that we could ever hope to replicate that fully in in a model systems there's always going to be a step where we need the animal research because I just if you just think of how for example an insect born virus is transmitted with insects blood feeding in the skin the skin is one of our is the biggest organ we have and is one of the complicated the most complicated organ we have and then you have blood vessels bringing all these cells and responding and then it gets distributed to the entire body this level of complexity would almost be impossible to to to create in an artificial situation and although you can take it so far and reduce the numbers which is the ultimate of goal there will always be questions where we need the whole organism. So currently the work we do on blutang virus we use about 20 to 30 animals a year occasionally when there is an outbreak of blutang virus for example in in a country where it has never been or there's a strain which is emerging which we don't know then there is the potential to do like an emergency study to be able to characterize the pathogenesis of this virus and to foster vaccine development for this particular strain. There are several vaccines against blutang virus and to understand why we are still concerned about developing other vaccines for blutang virus we need to look a bit at this virus so the virus has 27 serotypes so far we have discovered at the moment but they keep finding more and the problem we have is that the protection or the immune response upon either infection or vaccination is serotype specific so what that means is if you vaccinate against btv8 your sheep and your cow is only protected against btv8 it is still susceptible to 26 other blutang strains so the vaccines which are available are in northern Europe in activated vaccines that is they are safe and they are efficient and they have been used successfully to for example eradicate blutang virus 8 from the UK a few years ago but they are only they are monotypic so they will only protect against this strain hence they are fine in a situation where you combat a single strain incursion it gets more problematic when you're in a country which has several strains of blutang virus circling one big area for the research is to try to find out how can we get a cross serotype protective vaccine because in countries like India where blutang virus still has a big impact on subsistence farmers especially in the south they have 10 15 20 strains of blutang virus circling so a lot of endemic countries use a modified life attenuated vaccines so they have several strains of life virus however it has been shown that they can reach levels which makes them transmissible so midges can actually pick up the vaccine strain and then testing some of them in British breeds they also induce clinical science so while some indigenous breeds have clearly evolved with the disease and do not get sick to these vaccines anymore we did not use them in northern Europe because we could show that to certain preparations they would still induce clinical disease in in the country so then when we test for antibodies we don't know does this animal have antibodies because it got vaccinated or does this animal have antibodies because it was infected at one point during the life so that makes control very difficult and then another area with inactivated vaccines is although if they are applied well in time they protect against the challenge of the virus the immune response is relatively slow so an animal is protected a sheet probably after three four weeks cattle at the moment need two dosages so that would mean probably six weeks until they are protected so if you think of an emergency vaccination where the virus is already active you could find yourself in a situation that induction of immune response isn't quick enough developing better vaccine which might be quicker might again shorten that risk if you need to use a vaccine preparation as an emergency response so these are all drivers for improving the vaccine although in a in a one-strain outbreak situation and applied well before the virus really gets going the current inactivated vaccine available for blue tongue will protect your animals and and is a good is a good way of protecting your animals another very important component of this virus which is crucial to understand is that it is segmented so its genome is arranged in segments and what that means is if two strains of blue tongue infect one cell they can swap segments a bit like influenza can so we create this virus not only creates variation by mutation it creates variation by changing genome segments which we call reassortment the immune response to this virus is monotypic so it is specifically to the serotype other characteristics however a strain specific so we can have a mild or moderate or virulent strain of for example BTV1 so when we have a new outbreak we by serotype have no clue what this strain is going to do just because it's a BTV8 strain does not mean it will be a virulent strain we have to monitor we have to see and sometimes we even have to do an animal experiment to understand which what kind of strain are we dealing with is this a virulent strain is this a mild strain how quickly do we need to get a vaccine out or if this is a mild strain can we let this go and this can obviously change very very quickly with reassortment so you could have a mild BTV1 strain circling and a virulent BTV8 strain circling and then they infect the same animal and suddenly they swap this genome segment which is responsible for the serotype let's say BTV1 but then the virulence is on other segments and suddenly you have a new BTV1 because your BTV8 strain has now got that segment from BTV1 but it has remained all the virulence of the other segments which inside really make it BTV8 but on the outside it has now become BTV1 however it still does mutate and it does mutate in this segment this segment too which encodes for the outer code protein which defines the serotype and this is why we have 27 serotypes but the strain landscape is far more complex because it can chop and change all the other segments and therefore render a vaccination campaign useless within the exchange of one genome segment