Vaccine Manufacture | Spring Into STEM

so just give it a few more moments and then i'll explain how the how it's going to work um in the meantime a very very warm welcome um jasmine and i have met before this and we were both very excited about doing this session um over the last year we haven't had um many opportunities to engage with undergraduates and we always really enjoy these sessions it's the second year in a row we've done these and we're very much very much looking forward to welcoming you all here online to ucl so um so we're on one o'clock so i'll just explain um how the system is going to work so if you have any technical problems at all please put in the chat if you can't hear us clearly or there's any kind of problem with the video then please let us know and we'll try and solve your problem that way you can ask questions throughout the session um at any point there's a q a box you can put a question in there um we may wait until the end of the section that we're we're in to try and bunch questions up together um or you know we've got thematic questions that seem to be asking similar type of things or if somebody's asking a question that's easier for me to answer in text and put a link in there i may do it that way but you can ask a question at any point and you can ask it anonymously um we've got two polls that we're going to launch we'd just like to know whether you're interested in undergraduate postgraduate study or neither and whether you have an offer to study with us just so we've got an idea of our audience from this point and at the very end of the session we'll send you a link to a webinar so what i'm going to do now is i'm going to hand over to professor martina nicoletti and um after that we're going to have jasmine um and as i say ask questions throughout but we may wait until the end of that section before you answer if i turn my camera off i am in the background so i'm here answering your questions over to martina right so can you see my slides correctly yeah great okay perfect um so i my name is martina i'm one of the professors in the department of biochemical engineering and today uh yeah it's a pleasure to to be here what i'm going to do is just to give you a brief introduction to a little bit ucl department leading to our work in the vaccine manufacturing space um and then yeah introduce one of my researchers dr jasmine samaras who is going to you know provide an example of her exciting work um but first something about me so you know who you're going to talk to who you're talking to now and who you're asking questions to um i'm from italy as you probably uh understand from my accent i have done my studies there i had always i always had an interest in in the bio side of things but in italy wasn't available as a first degree um but i did have the opportunity within that to visit and what to spend a few months um in birmingham um as part of my degree and and there i was working um as well for for a company for for a period working on um some some bacterial some bacterial work in bioreactors which was you know which really fascinated me i um then was offered a phd so i did a phd in mechanical engineering so you see how my background is really sort of multi-disciplinary already although really focusing on the engineering fundamentals at king's college and it was a great experience where i really i realized that research was for me and again there i was you know again focusing a little bit more on the what we call upstream processing and specifically reactor works and reactive fundamentals um so there was a position at ucl so he was at ucl as a postdoctoral researcher and i've been here since 2004. first i was working in interdisciplinary project with different biochemist biologists and chemists which was amazing and and then i joined as an academic staff member in 2007 and i became a professor a couple of years ago my interests now really focus on engineering fundamentals so in the department we have different staff with very different expertise so those of you who attended uh doigo's lecture um she is you know as well an engineer an engineer focusing on really the modeling side i'm an experimentalist and the rest of the department is really again comprises you know staff with expertise in the life sciences as well so quite a mixture so so as i was saying very focused on the engineering and especially the impact on the environment on different cells and the product i have applied my the portfolio of techniques that i have developed for you know looking at the aerodynamic environment to different types of products in both the cell engine therapy space to biopharmaceuticals and more recently to vaccines in the department each academic staff member has different roles so um for those of you who who will join us next year i will also be your departmental tutor so essentially i'm responsible for pastoral care in the department but also have this role of overseeing a number of different matters and your experience at university from the time you join after admissions during you know the teaching assessment and communicating with you with the students most effectively um so you might have you know researched about um ucl so i'm not going to spend too much time um focusing on on these we are but those you know for those who joined who joined this uh stamina for you know is one of the first so we are in the faculty of engineering science um is very successful for grant funding recipients what does it mean it means you know we do lots of research that actually actually has an impact and we are successful with that um in the department you know first department of its kind and we are again focusing a lot on different applications and cutting edge applications um and have quite a a strong a strong researcher research and teaching base here so something more about the department um we consider ourselves as one of the largest academic by process group in the world who's focusing mainly on really bio processing rather than you know proposing this only has a side as a side sort of research topic we are indeed a small department they are much bigger engineering department um so our intake for example at undergraduate level is around you know 40 50 um students but we you know we're very happy with the you know the type of stuff to students rachel that we propose um large cohort of doctoral researcher and postdoctoral and i think we are also very you know proud to uh you know to be um you know really like family and very friendly uh environment definitely multidisciplinary and a team based approach we have a lot of academic and company company collaborations so we have a number of uh different hubs and i'll talk about one of these uh in a second to introduce the vaccine space which you know students really benefit from has everything we do really is expands into our thought programs and research projects uh as well for undergraduate and postgraduate programs um so what type of um research do we do and what type of products do we do research on so approximately department is divided into three different areas the industrial by technologies which you know works essentially when working on complex chemicals um better pharmaceuticals but also finding solution for finding environmentally friendly solution and we work on biopharmaceuticals so different types of therapeutic proteins uh gene therapy working for different viruses and vaccines is belongs to this to this category and then celengene therapies that you might have heard the from so really stem cell uh the stem cell work and gene therapy work as well and some of us have got expertise that actually goes you know spams across all these different uh this different area one of these area is boxing which we're going to talk about today and it's something that i embraced recently as i'm the director of one vaccine manufacturing research hub would say harbor is really like a group of researchers so we have this sort of large grant which funds researcher and the it's very difficult environment to be in uh the landscape for vaccine manufacturing is that is really limited investments and when i say traditional here i mean before the pandemic as a lot of things have changed after limited investments it's really the process development for for vaccines is complex and therefore costly high risk of failures many times for a vaccine against the specific pathogen we have to develop a new process as i say manufacturing is is complex and of course there are you know uh in association and alliances like gabby negotiate united um you know within the united nations you know they they essentially negotiate uh quite a low price for um per dose so really we need to bring the cost down to the cost of production so within this context a few years ago me and sarah that you might have a certain professor gilbert from from the general institute in oxford you might have heard in the news as one of the leader of the of the oxford astrazeneca vaccine we essentially are the co-directors of this back sub and we have worked with different companies and different low and middle income companies members and as well as other partners on research so what do we do we look at developing scaling and manufacturing vaccines for the benefit of low and middle-income countries so this is to ensure that we have supply of these essential vaccines we work with manufacturers for example from indonesia from india from vietnam to ensure that these advances are translated to you know the technologies are translated to manufacturers so they can do their own production and we propose technologies that are able to support epidemic and epidemic threat so because you know and as i say this is the proposal that we did prior to 2018 so well before the pandemic and it is really can we have responsive technologies that are able to respond to different type of epidemic scenarios and of course some of these technologies then turned out to be quite good and beneficial um you know to prepare and to to to produce a vaccine against the current pandemic so this is our team ucl and oxford but we have other different other academic partners in different universities different university university of leeds imperial and london school for hygiene and tropical medicine so this is about some of the research in the hub that as i said perma aids throughout the thought degrees we build on the fundamental first and then we have full courses uh in the final year for you know vaccine on vaccine value processing which is i guess the most relevant to this topic um and on this note i'm going to stop sharing here and um introduce one of my researchers um this is jasmine samaras so if you can share she can share her slide and she is she's been she was in in our degree and she is um in my group so she's been with me for a phd and a postdoc and she's going to and now works in in the in the back sub with the london school for hygiene and tropical medicine and she's going to explain a little bit more about uh you know what she does and what's the uh you know really the excitement of the uh of the new technology that we collaborate with uh with the london school so it's interesting just before just before we start jasmine just to say we've had one question come through um we'll keep that until the end because it's a really really good question but anymore please bring them in i'm also just about to launch um a poll so if you just fill that in as we go along will be really interesting thank you insights interrupt um okay okay so thank you martina for your introduction uh hello and good afternoon everyone that's joining us today thank you for taking your time and joining us and i'm going to be giving your taster lecture on vaccine manufacture i hope you find it informative interesting and maybe see something that you like and want to take forward in your careers so um just my name is jasmine samara so i got my masters and my phd both in the department of biochemical engineering here at ucl working with martina and my phd was sort of looking at combining the field of engineering with stem cell research so we were looking to improve upon the current yields um for stem cell repair specifically looking at repairing the heart and that was a collaboration with ibet which is a research laboratory in portugal so i actually got to go over to portugal for my phd which is really cool i'm now currently a research fellow in the department so i'm working on vaccine research as martinez said and using engineering kind of know how to improve and and try and help um vaccine manufacture processes so i guess this kind of takes me on to the end of my presentation i'll give you a little bit of an overview of the work that i'm doing and how that relates in general to kind of undergrads and if you're coming to join the department so why is that not changing slides now okay so vaccines are really vogue at the moment they're gaining so much attention all around the world with the outbreak that's happening around us and what is often forgotten is the historic origins of vaccination so where did the word come from how was it discovered so for this we remember edward jenner which coincidentally is where the oxford team responsible for the now astrazeneca covid vaccine got their namesake so in the 18th century we were played with a virus known as smallpox which caused approximately 400 000 deaths a year which doesn't sound like as much as what we're seeing at the moment but in those times there was a much smaller population in the world and it was quite a significant number of people and a third of all survivors were going blind so it's not a very nice disease and general observes that milk maids in his local area had been previously infected with mild much milder cow parks and then appeared to be protected from smallpox so he kind of experimented a little bit with this idea and found a milkmaid her name was sarah nelms um who had fresh cowpox lesions apologies for the uh for the image it's kind of gross but just to give you an idea of how it looked and he used a sample of her wounds to deliberately infect an eight-year-old boy called james phipps um he then recovered from cowpox which he was indeed infected with thanks to jenna um but then when he tried to infect the boy with smallpox he found that he was protected so the latin word for cowpox is vaccinia so jenna decided to call his new procedure vaccination and thanks to this discovery naturally occurring smallpox has now been globally eradicated so thank you jenna so what is a vaccine by definition a vaccine can be any component or preparation which can be used to stimulate an immune response and these components that you kind of prepare are called antigens so vaccines create immunity by introducing either a weakened inactive or a subunit of a pathogen that makes us ill such as bacteria or viruses the acquired immunity from a vaccine essentially then prepares your body to mount a defense when it encounters the real disease-causing agent so before covid the world health organization or the who um roughly estimated that there were between or at least two to three million people saved each year through vaccination programs so vaccinate vaccines sorry vaccine preventable diseases um include things such as rabies flu tetanus cholera hepatitis b bacterial pneumonia and measles and of course covered 19 can also be prevented with vaccination and disease variants are then another matter and may require for example a new vaccine which is what we see um for example with the seasonal flu jab that every year is rolled out uh at least in the uk i i can't speak for all the other countries that have joined us today and so thinking about the typical vaccine timeline a vaccine from initial discovery in a lab can take anywhere up to 15 years before it is then approved and reaches the market so this encompasses the initial research phase when we are dealing with thousands of different possible vaccine candidates and to then progressing through to pre-clinical and clinical phases where fewer and fewer vaccine candidates are screened things like safety efficacy long-term impact and dosage as the number of vaccine candidates decrease the number of participants in the clinical trials increase but then coincidentally so does the cost if we consider the overall cost you're looking at anything between 500 million and up to five billion dollars per vaccine which is just an incomprehensible amount of money and it varies so much with manufacture the vaccine itself that's been developed the country that it's developed in and facilities do we need to contract out manufacture there really is quite a lot to consider um so during an epidemic or pandemic scenario these timelines are hugely reduced um as we have seen uh in roughly 12 months from discovering the virus the oxford estrogenical jab for example um was approved in the eu in 12 months when you're looking at this kind of normal timeline of 15 years that is super impressive so a vaccine can take one of many different forms the design is predominantly dictated by the nature of the pathogen and how it affects us as well as practical considerations such as uh how the vaccine will be used most common are live attenuated vaccines where the infectious is the infectious agent uh is altered to be less harmful and in a kind of weakened state and inactivated vaccines are another of the most common where the infectious agent has been killed and then there's also subunit vaccines and which essentially just injects a portion of the infectious agent so generally speaking um subunit vaccines are considered to be the safest and also the most efficient of the three i also thought it'd be interesting to highlight the three currently approved covered vaccines in the uk so the auspic oxford astrozenica vaccine is a viral vector-based platform where essentially genetic constructions of the coronavirus are transported into the cell via a weakened virus delivery system the pfizer and moderna vaccines are mrna vaccines which again provide genetic instructions to the cells and just without the viral delivery system that your oxford estrogenical jab uses so in the context of my research i'm going to focus on conjugate vaccines which are essentially a type of subunit vaccine sometimes just using a subunit of an infectious agent in a vaccine is not enough to get a sufficient or a long lasting immune response so to improve this we can combine this weak component or a weak antigen with a stronger immune boosting antigen and create what is called a conjugate vaccine so a good example of a conjugate vaccine are vaccines targeted against pneumonia which is caused by the bacterium streptococcus pneumoniae so there are 90 different forms of this bacteria that cause pneumonia which are called serotypes so luckily for us only a few of these stereotypes actually account for most of pneumococcal disease we don't see all 90 affecting people to the same extent so the diagram on your left shows the bacterium streptococcus pneumoniae with some of its kind of main features highlighted you'll notice on the outer layer there are these kind of branched fluffy looking chains and these are called polysaccharides which are essentially just made up of sugar molecules and so vaccines designed again designed against pneumonia target specifically this cell surface polysaccharide which is specific to each of these 90 different stereotypes of of the pneumococcal disease so the vaccines against pneumonia are either made up of just this polysaccharide unit which is essentially partially protective in adults and not for as long a duration or they can be coupled or this word conjugated to a kind of protein toxoid component which essentially just makes a more potent vaccine and makes it much more effective in the elderly as well as children who have more kind of naive immune systems so these pneumonia vaccines are a lucrative business so in 2019 uh pneumo vax 23 which is manufactured by merck made the company 334 million dollars so this is a polysaccharide only vaccine so it's best suited for adults and doesn't necessarily offer good long-term protection when used by itself um but as the number of at the end of its name kind of suggests it covers 23 of the 90 different serotypes of pneumococcal disease prevnar 13 which is manufactured by pfizer is a conjugate vaccine so it's made up of the polysaccharide component conjugated to this immune boosting protein component now this made a huge 5.95 billion dollars in 2019 which is serious money but pneumococcal disease is still a pretty big problem globally in 2017 for example pneumonia was responsible for the deaths of 2.56 million people a third of these were below five years of age so despite there being these you know these vaccines available on the market they're not reaching all of those that need the most and this is largely related to the cost of these vaccines so the reason that they're so expensive is mainly down to the production process that's necessary to manufacture them so i'm going to focus a bit on previous 13 for example so this is made up of 13 different serotypes which means that in manufacture we need 13 separate cultivations to produce the polysaccharide for each stereotype each of these must then go a purification process um which although simplified on the left is actually quite a complex and multi-step process so on the right um you can see the kind of all the steps so in our degree programs uh you'll study each of these individual unit operations learning what they're for when to use them and even design your own manufacturing process for different applications maybe one like this so each of these individual sets so you've got centrifugation filtration chromatography they all cost money to perform and each of these steps will result in a loss of your yield now a loss of yield means a higher cost at the end because you're getting less out of it from what you start with in addition to this so in addition to these 13 steps already that need to go through all of these steps in between and we must also separately cultivate this immune boosting protein component which again means its own chain of purification steps before it can then be combined or conjugated with this polysaccharide component so once you've combined the polysaccharide with the protein you then need to go again with another purification chain to finally get this product to meet the requirements to be a vaccine so imagine doing three huge purification chains 13 times and you can kind of begin to understand why this process is so expensive so the complexity of it is even it's only made worse when you factor in quite often these steps are not all done in the same facility they're done by lots of different scientists so you also have to account for things like storage transport and also you know you're maintaining ultra sterile conditions here because this is at the end of the day a vaccine is going to be injected into healthy people and it is just expected so this you know why can't countries afford this vaccine because prevnar 13 can cost anything up to 179 169 sorry 169 dollars per day that's huge so luckily and martina kind of mentioned uh these guys in in her talk as well there are global alliances such as um the global alliance for vaccines and immunization or garvey and which actually aim to subsidize and make vaccines such as previous 13 and more accessible and affordable for low-income countries the map on the right shows you the countries that are eligible for gabi support those that can and do benefit from garvey can access prevnar with reduced pricing with anything as low as three dollars per days which is great um but there are still quite a few lower and middle-income countries that lose support of garvey who still can't afford this vaccine which is countries such as um angola bolivia indonesia sri lanka just a few for example so we clearly need innovation in this space we need something new and that is some of the work that myself and my colleagues at ucl hope to contribute to is it going to change okay okay sorry um so really promising alternative to the current manufacturing process is a bio conjugation method where the conjugate back vaccines um are actually produced and kind of conjugated or coupled inside the cell of e coli so you've all heard of e coli perhaps more for the wrong reasons and the right reasons but in the world of pharmaceutical manufacturer or just in general kind of more biological world um e coli can be engineered pretty easily to be a powerful workhorse and in this context it can offer a significantly simpler production process for conjugate vaccines oh sorry i think i leant on my mouse there we go um and in doing so it can offer a yeah a really good alternative to conjugate vaccines and hugely uh reduce the cost and let me show you why so um if we envisage the production process for these bioconjugate vaccines where they're expressed in e coli and first the actual cultivation and combination or conjugation of the polysaccharide and protein components are all done in a single step inside the e coli cells what so all we have to do is cultivate and grow e coli then instead of these three separate purification chains that we were seeing before to get our product we only need one purification process to go from this initial cultivation of e coli to our vaccine so less process steps is basically less material cost quicker production and significantly you know less losses in your yield so hopefully this should give us a much cheaper product so there are some products that are made in this way using this technology this bio conjugation technology which are in clinical trials um but this is still a relatively new technology still a new idea and there are no vaccines commercially available that are made in this way so how do we speed this up and how do we get this to market because this could be you know fantastic for the world to have um so coming back to our vaccine development timeline and myself and my colleagues are currently in the early research phase with our pneumococcal bioconjugate vaccine so this means that we are still optimizing production as well as the product and therefore have thousands of different combinations and vaccines to test yes so in the department we use a number of different tools for bioprocess development the first example is miniaturization so when we cultivate e coli to produce our conjugate vaccine this can be done in ever in a number of different ways in different volumes so the photos that i've got up on the slide and are just some examples of what we would use and what we have in the department so on the right is 100 liter bioreactor where we can control things like ph oxygen temperature and stirrer speed and as you can see it's quite a large piece of kit so useful when we want a pilot version of a commercial-sized vessel but a lot of work to run and a lot of material it would be needed um especially if we're thinking about you know we need to screen thousands of different vaccine candidates to make so going along the left going along from right to left and other vessels that we can use in the department going down in volume sizes and and also just kind of simplifies the research and speeds it up the smaller scale that we go so all the way down to micro oil plates on the right hand side where we essentially work at the micro scale and culture in parallel on one plate for example 24 96 or 364 conditions at one time in each of these individual wells so the ability to mimic behavior at different volumes or scales is a huge advantage in the world of research as it can really speed up the screening of different vaccine candidates and it costs much less when you're working in such small volumes in the department we miniaturize many different operations so here are another two examples on the left we have a miniaturized version of a centrifuge which is used during product harvest and purification and on the right is a miniaturized version of a filtration system again for us to kind of test different uh conditions different filter types for example so the main benefit in general of all of these kind of miniaturized systems that we use is to help us predict the outcome of what occurs at larger volumes based on the performance in the smaller volumes and it's a lot easier for us to work with so in the context of my research i have worked on cultivating our pneumococcal conjugate vaccine in small bioreactors up to 200 mil volumes on the left hand side and down to two ml volumes on in the microwaves on the right so being able to produce our conjugate vaccine from e coli in both means basically that i can test loads of different things in parallel in super small volumes on the plate on the right and then i can use this to predict the performance and how it will be in much more complex and slightly larger volumes in the bioreactors on the left so in the middle i've put like a colored representation of our conjugate vaccine that i've produced in the lab both from the microwaves and the bioreactors so the polysaccharide component of the vaccine is shown in green and the immune boosting protein component of our vaccine is shown in red so you can see there's a hundred fold difference in volume between the microarrays and the bioreactors um and the amount of vaccine which we quantify in this in this image by the band intensity so how bright that color is and how chunky that band is and you can see they're pretty much the same which basically shows that i've got a good representation in the microwaves of my bioreactors between the two scales so it means that basically i can use these micro oils to test my thousands of different options and different vaccine candidates which is which is fantastic it's such a powerful tool um so another really powerful tool that we use in our research and i hope these videos are working for you because it's much more interesting excellent it's much more interesting to see videos than to have me talk about it and we use automation and uh or robots basically so i prepared these videos just to show you some of the automated process and the real advantage of these is the efficiency and repeatability of the work that is done on them so the accuracy of the research is hugely improved when you take out the possibility of any manual error and again whilst you're screening thousands of different vaccine candidates in for example these miniaturized formats that i showed you before and it's hugely beneficial when the alternative is you know working manually or 24 96 or 364 different conditions at the same time so it really does save my hands a lot of work um and you know as technology is improving all the time automation is it already is and will continue to gain huge amount of traction and being able to learn how to use it and program these systems uh really is such a unique skill and it's pretty sought after and so during the undergraduate and postgraduate courses students do research projects and they can for example learn to work with systems such as this on different research um projects as i mentioned which are designed by post-doctoral students so phd students um or with researchers such as myself for example so coming back again to my work more specifically and the combination of miniaturization and automation the implications in terms of vaccine research it's just so invaluable when you're having these tools and applying these tools so my work i have used this combination to test different strains of e coli that make our vaccine and i've tested different nutrients that i grow the e coli in and also looked at different combinations of this immune boosting protein component with my pneumococcal polysaccharides so we are in the early phases of research but to be part of you know part of this journey that is bringing these products to the market and the impact that they could have eventually is invaluable so the tools and research that we do i guess is just a stepping stone in reducing the number of vaccine candidates to test but our courses are a stepping stone to joining in with our research so thank you all for your attention i hope i haven't bored you too much and uh hand over to kim for any questions fantastic thank you thank you uh thank you very much that was great i enjoyed that what i could watch because i was also keeping an eye on the questions which are brilliant so what i'm going to do is i'm going to invite jasmine and martina to school scroll through the questions in the q a because some will relate to clarification some things that you were saying um and others are questions which you might want to group up together so if i leave you to look through the questions please put your questions i can see they're coming in thick and fast which is great um but whilst uh martina and jasmine looking at those i just want to remind you um there's another poll that i'm going to launch here i'd like to know if you are um no so that's fine um forgive me um i've noticed that some people are undergraduate some people close post budget if you're interested in studying msc biochemical engineering with us professor dan braisver will be available for a q a session coming up so i'll put a link to that in the chat if you want to sign up for it you can ask dan about the process of doing that if you're interested in selling gene therapy not only have we got a cell and gene therapy taste the lecture coming up we've also got a q a session with christine so you can actually ask him if you want to know more about applying for a program um so i just really want to mention that those are coming up and finally i know that a lot of people are interested in studying a degree with us or elsewhere at ucl there's a ucl undergraduate open day happening um on the week of the 14th of june we're we're gonna be there on the 14th of june you can come and talk to uh dr bren uh ben parker um there's also going to be chica there's going to be fiona so we're going to talk about the program you can talk to our careers team any questions you've got you want to know about the programming more details we'll be there for that um and i'll put a link in the chat so that you can register for that as well um so uh jasmine martinez if you answer the questions if you click answering live then we can sort of move them across and we can try and get through them as we go through um but i'm going to hand over to you so you've got a lot of questions so we don't get through them all um apologies we've only got a certain amount of time but um i'll leave it to jasmine and martin to go through them thank you okay so it was um i was actually reading some some of them while while jasmine was talking um so um i can't see myself in the video so hopefully you guys can can see me so um now i'm gonna start from those that were posted uh first so just in the order in which they they were posted and what i'm looking at is the really q a box i know there are some in the chat maybe i can go through uh some of those later so um there's a question about capacity of vaccine production before and i guess after or currently right capacity of vaccine production now this is a a nice question but it is complex to answer without knowing uh in which country obviously the capacity really uh changes a lot but in the spirit of the other questions maybe i can understand background so in the uk i mean sorry in in the world there are some um very big uh vaccine producer companies with lots of expertise not necessarily in the same vaccines which are where which are gsk merck pfizer and there are like some medium and um smaller size factories and as well the um so in the capacity of vaccines per country as i said really differ and per continent i would say really differs i think um the pandemic has shown you know for for some of you that have followed the you know europe and you know the european situation for example you know has definitely highlighted that uh it was it was quite difficult to find for example production factories um um in europe right um where astrazeneca could essentially contract manufacture uh the uh the assassinica for the astrazeneca so it's uh so it is it is really varied um in terms of low and middle income countries if the question was hinting at that is asia you know we work with manufacturers mainly in asia and they have a very you know quite quite this is quite good production the biggest vaccine manufacturers in the world is uh actually in india and this is serum institute of india so although probably not very you know no no well known right the number of the the names i've mentioned before are sort of you know big by pharma who with with expertise in in vaccine syrum institute only produce vaccines so so i would say that the capacity really changes it does it has a changed slightly meaning that with the pandemic well before it was really difficult to obtain investments in the vaccine space now it is um obviously uh you know there has been lots of investment and there is lots of interest um so i would say that yeah now there is a bit um uh yeah this is the highest this is higher you know the vaccine and the production size are higher in the in government's agenda so this is how i would answer the question um so there are um vaccines are based on inactivated some rna cyan viral vectors right the current carbon 19 vaccines and the question here is asking whether um which approach is easier to must produce and which one is best for to address variants so very difficult question so it's um inactivated various i would say that there are like more um it's more traditional manufacturing and there are more issues with the um with the safety rna um easier to scale at mass production but very new technologies therefore let's say that the cost on the cost side is higher viral vector there is a few products there on the market and i would say is a little bit in between and price is definitely lower than than the rna for example in terms of the variance uh this is more of an immunology vaccinology questions which i'm not sure how if i am the best place to to answer but what i've heard from colleagues is that in any of the approaches is this is quite difficult as it would require as you would require a change in the original molecule and therefore then you know further studies in process development to support manufacturing a lot of these are happening in the uk for example this is what i know and work against viruses have been you know i started a few months ago but yeah they i wouldn't point to to one which is easier than the other another question is can you explain the process of all inactivated or and live attenuated how can manufacture ensure they are safe such as the virus yeah so this is a question again for uh more of an immunologist rather than rather than an engineer if jasmine would like to read the questions and can provide further details i would appreciate this is i think the third questions on the qa box um in time i'll go i'll go along with with the others so this is something really this is another question which i was really keen to answer which is uh compelling and it says you know average time for approval for a vaccine you know between manufacture development manufacturing approval is 15 years you know lots of people are worried about the urge the the um how little you know how uh quick sorry how quick was the release of the kobe 19 back since and whether they have they're linked to obviously uh side effects in the future because maybe something has been um you know overseeing et cetera so i think i would i would mention some important things the investment and the attention um because of the global health emergency has been incredible and the uh so for example imagine the full you know full teams of vaccinologists immunologists you know they left whatever they were doing and they focused solely on trying to develop a a vaccine against covet and this similar happened in groups in in different companies they dropped other types of you know vaccines they were manufacturing to focus on this so there was a really a very quick reorganization coupled with a significant investments and and this has made a great great impact you know in terms of speed at which you know we could get a molecule in which we could get the process there um and um yeah and and the regulatory approval the regulatory approval is is not a full approval uh which was what jasmine was mentioning you know in terms of the 15 years this is in approval for emergency use which is a little bit different and in the pandemic the regulators were in contact with the groups throughout the clinical trials so they didn't receive data at the very end right they had you know all the data um alongside the process just to speed this up another thing i'm very keen to say is there has been an unprecedented uh collaboration worldwide between different academic groups with different expertise and industry um brought you know together by the pandemic so um which i've noticed which i think is um just like to ask because somebody's asked whether you'd need to um they've asked the question they've actually asked is um would you be expected to uh understand this if you're in first year so can you just explain the context of the presentation jasmine if this is you know what sort of level it's at to to reassure someone yeah so i mean i guess um as a first year you have from what i remember it's been a while since i did the undergraduate course but you do have immunology lectures you do learn about the basics of different vaccine types you learn about how they infect your body and the reaction they have on your immune system you might go into a little bit about the different types of vaccines so when i was talking about the live attenuated and the uh holding activated and you'll learn what the differences are and what that means and going into the kind of more nitty gritty of the manufacturing side it's kind of tied in as you go over the course you learn about the different unit operations that are used to culture to purify and you learn about each of these in more detail as the years goes on i'm not entirely sure if that's in your first year per se um i think a lot of this talk obviously would mean more the more you go along in your projects um i i tried to make it a bit more so that you could understand it without having studied in this area or at least get an appreciation for some of the kind of aspects that we look at and and the problems that we're facing as well i guess i would yeah i would add that this is the level of this talk is really for a final year bsc students in the year three or a uh our level seven which is that the final year of an image degree just because of where things are placed in our degree they would be able to really sort of understand uh you know the broad spectrum of you know from the sort of immunology to the process to the issues in manufacturing yeah um there are other questions i don't know jasmine if you if there is one there are some that are referring particularly in particular to um what you have discussed so just feel free to interrupt me if if you want to answer the question um there is another question from you know colinet that was related to what i was talking before so the timeline for vaccine manufacturing and depending on the urgency of what the vaccine prevents or funding and you know am i yeah i think i've enhanced that in terms of you know this being um probably both um there's another interesting question how fast does it take to retool i think i guess uh change a vaccine uh production vaccine production before oh sorry i'm sometimes not lost my question okay how does it take to change a vaccine production facility to switch between different types and this is really difficult this is what i was talking about before if every vaccine needs a bespoke process development then you'd need a you know some of the tools might be the same right but um but it really it really depends right and i'll give you an example some vaccines are bacterial vaccines so and are you know you need to actually grow a bacterial organisms in other cases like the vital vector most of them are made using mammalian cell host so you would not be able to grow those two organisms in the same reactor if the bioreactor is made of stainless steel and you know when i before i was referring to new technologies the responsive technologies you know is is something that we do lots of research on there are new by reactors which are essentially with the bag which is a single use that is abe where you know we are able to use exactly the same infrastructure and just change the bag and that would greatly facilitate and go around this problem right um of you know possible cross-contamination and reusing the infrastructure possibly for multiple uh for multiple products right you know switching quite quickly between one and the other and as well with this with this question quite often um pharmaceutical companies will kind of stick to their existing processes that they have so it is more from a money perspective you know the time and effort that it takes for them to research new methods of purifying or new ways of cultivation you know if something works they're not going to spend that time and money to change their process so quite often they'll stick with the same process where they can whether or not it's for the better or for the worse in terms of product yields and and that's where the kind of vax hub or the hub that i work in and martina leeds and one thing that we wanted to look at was creating these platforms that can be used for different vaccines but still maintain good quality of products and and high yields as well because a higher yield means a cheaper price per days yeah i'm going on with the with the questions here so there's another question with the you know emergence of again the variance pieces what are some of the strategies that we can adopt for development of vaccines we can keep up with the speed of the virus mutation very you know very difficult and you know as i say there is a lot of immunology work that needs to be done um in terms of speed though from an engineering perspective some of the tools that jasmine has illustrated like working at a very small scale working in an automated fashion allow us to do lots to screen for example right lots of different uh types of strain right if this were available from you know the cell engineer um at the same time and optimize it quite quickly so i would say that some of the tools that we are yeah we are working on are exactly you know aimed at speeding up process development there's another question on edible vaccines so it's not something that we um we are we have studied here we have worked on and this is where essentially you make some gene modification to a plant um so that i think it produces some sort of subunit um structure and i think i mean i i think that they look really promising this is our my thoughts and is um especially for countries where you know this some of the some of the the vaccines really you know are not stable at you know at room temperature and they need fridge etc you know they would make transportation much easier um so i i i think and i hope lots of research is done on that is not specifically our you know we don't have collaborators right you know working on on on those but it's definitely you know very promising for the future i would imagine also to add on to that martina i was talking to one of my uh colleagues in the department and they mentioned to me on the field of you know edible vaccines that they were working with algae and they had actually produced a vaccine in algae that was for sap i think it was for salmon and basically the salmon eat this algae which contains a vaccine and they were able to vaccinate all the salmon so although you know not for people but still this kind of idea of an edible vaccine and that's something that's going on in our department so that was really cool and another example of some of the research going on yeah yeah yeah yeah that's true i was forgetting brenda's research on on algae that could go in very well in this uh in in this direction um let's keep on maybe for for a few more minutes um there is a there are some questions jasmine on the raw material using the pneumonia vaccine manufacturing um and approximately the time i don't know if you want to like to answer that i actually don't know how long it takes for them to the the time that it takes for the provenance 13. yeah so um just yeah maybe i can i can answer a little bit so the the raw material so the our difficulty in case of the prebna is that uh everything is um uh everything is confidential so for example i have a separate project is separate to wax our project with fisa on on this blockbuster vaccine that they have resolving some challenges in the in the process and and even as part of that collaboration which obviously is uh with the legal agreement um you know i know i you know i know very little about uh you know this this type of questions like you know what are the materials as well as what is uh uh as well as what is the time but you know you think that you know the starting material for the production of the polysaccharide and the protein is a um it's a bacterial if a bacterial fermentation which is basically within a day but then following that there are a number of different steps of purification which you know where you know in between those materials can be stored in the fridge if they have tried and you know and that's okay and it's stable um and so i that particular process is probably involving thousands of scientists and multi-sites um i don't know exactly you know you know that to start from finnish my guess would be you know once you have the two produce you know the two polysaccharide and and the protein would be in the order of weeks uh but yeah that's that's all my guess so um so we have another question of raw materials used in the pneumonia vaccine in fact no sorry let's just sorry i think skipping so how is it vaccine design process like do we start with a detail well-defined molecular structure and then use different manufacturing to make well it's so there is an initial stage where you know there are like expert like vaccinologists um that they essentially work on the you know the initial stage to uh to make a developed molecule for example in this case like in the viral vac vaccines and the astrazeneca the strazenica oxford one um they focus more on the on the actual uh the genetic manipulation of the virus and do initial small scale experiments to um you know to ensure you know to for example to characterize the uh the structure then um after that that you know the way in which it is produced is by infecting mammalian cells so you need to have a quite a you know a good uh a good cell culture uh number there and it might take up up to two weeks then the the virus is inoculated to to infect those cells all these are sort of the initial the initial steps um that need let's say some some small scale experimentation to optimize it right to optimize the media for example to optimize the growth condition to optimize what's the good percentage of the virus versus cells so all of these will have to be optimized in sort of small scale sometimes flasks sometimes most skills by active fermentation um before yeah you then go to the purification steps um so i'm just aware that we've come to two o'clock so um if it's okay i feel really bad because we've we've got so many questions that we'd love to answer so if it's okay for martina and jasmine to stay on um we'll carry on for five more minutes and try answer as many questions we can if it's okay with you martine or new jasmine um but then we'll finish at five past because otherwise the recording this will be too long we'll be cut off at the end anyway yeah absolutely um i'm going just gonna scroll through questions and maybe talk about something yes find the questions that we uh we haven't touched on as i think there's quite a few um i'll give you a few moments to just scroll through the questions um i know that jasmine and i have been trying to type answers some some of them we just we just can't go into they're not really to do with manufacturing vaccines they're great questions but they're just not ones we can answer um just a reminder if you look through the uh the chat you'll find links to the msc open day the undergraduate open day there's a whole series of events that we're doing and i'll put a link to a survey we'd really appreciate your feedback we'd like to improve these we've even had a few ideas for future taster lectures so please do um get in touch with the softwares you will have my email address uh after this so you can always get in touch um but we'll try and get to a couple of your questions in the next three minutes yeah um right so um probably right yeah some questions i'm not i'm not sure because you know it just in the way in which they are they are phrased i don't think i can provide a very good answer i'd like to have yeah to talk to you essentially um so for example you know if we found the candidate that's been successful in trial how would you scale up the process another particular challenge that will be faced at this stage um so in um once so the clinical trials in order to do clinical trials they need to have the material needs to be already so you need to produce the material for the trial which is usually in you know relatively large quantities so this means that some scale-up has already been done before and it's already not only has been done at scale before clinical trials but it's already there is a you know the material produced for clinical trials in humans needs to be um it needs to follow uh you know the gmp compliance so it needs to be according to you know the the sort of certain regulations um the there are challenges in in scaling up so for example if you have a process that works perfectly at the latest scale uh this doesn't mean that you know when you go to 200 liter 2000 uh you know you you have exactly the same product and and they looking at you know correlations right where you can uh really uh you know have a very good performance a large scale you know for first time round is is something that in the department we we look at both in the upstream and in the bioreactor space as i was saying which is my research but also in the um in the downstream processing side um um let me find modeling i can answer the last questions about modeling is different from what we have talked about before uh it's it depends i think that there are um i don't i don't think that modeling plays a large role in terms of the in the first stages when you know in terms of the of the molecule and the immunology i might be wrong but this is what sarah sarah tells me so i i um i'll go with what she says uh you know it's it's um but maybe but then you know we have modeling we have modeling in the back sub so for example looking at how to optimize the supply chain right there's been lots of supply chain issues in the current pandemic so in order to make you know once the manufacturing process was ready for for a vaccine then maybe they were not you know the certain components needed you know some tubes some bags some probes to measure ph and oxygen etc you know they when they were missing just before because you know they were needed in in in quantities and the company was not able to produce them um so quickly so there were supply chain issues like that so some of the modeling that we do is looking at the supply chain um and also looking at you know the how can we best optimize the process based on the data available so that we don't do you know different uh you know then we don't try right so essentially to decrease the experimentation load and uh and try to to use a such modeling approach uh you know if they're science-driven and data-driven they are very they're very effective sometimes um there might be other questions that i'm able to answer i don't know kim if you know if you want i can spend a few minutes to just to type answer uh this afternoon well i'll tell you what we'll do um i'm just going to give you a moment if you pick the pick the three questions that you most want to answer um because we have to end it end it when it ends all the chat will go as well so we will pick two the two two most important questions um but one quick question of jasmine jasmine do you teach on the undergraduate program somebody's asked uh i don't teach no i assist mostly with um post-doctoral students so phd students um i kind of work alongside martina and help with their training or anything that they need for that in terms of the teaching um that's martina's job i can yeah i can i can maybe say final thing yeah so in in in our in our degrees they have academic staff and teachers and the body essentially do the main the main teaching so some of the experienced pdas and the doctoral students and supports us right supports us for example for projects in the lab uh yeah but yeah you will you'll be stuck with us i think and here uh thank you for your attention and really i'm sorry if yeah if maybe yeah i mean it's uh i mean we could only get through so many questions but they were brilliant questions they were really really good and i i have put a link to ucl minds coronavirus podcast you can uh you can hear far more about um martina's work uh about the whole sector you've also got susie for it as well professor suzanne freya who's a professor on our program and she's got some um fascinating things to say stephen morris we've got a lot of people who've been involved in that and you can find out a huge amount about what our involvement has been um so do check that out if you have the time uh finally um just thank you for your questions thank you for taking part um it's been really great to have you here and um finally thank you jasmine thank you martina um have a great afternoon very welcome thank you for the kind messages in the chat so have a great afternoon and we do hope that uh before too long we get to see some of you at ucl and get to show you around in person and answer your questions properly thank you very much bye-bye thank you bye you

2021-06-01 15:20

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