The Silent Epidemic & the Race for a Cure with TherVacB! | with Prof. Ulrike Protzer

0:00 Hepatitis B is a silent but devastating Global heart crisis affecting over 254 million people worldwide this viral infection which targets the liver leads to a staggering 1.1 million deaths each year primarily from complications like pyrosis and liver cancer while it is preventable with a safe and effective vaccine millions of new infections still occur annually with 1.2 million people people newly infected in 2022 alone in this episode we are diving deep into the science challenges and breakthrough surrounding Hepatitis B viruses are different there is no broadly acting antivirals yet um so we have to develop

0:45 an antiviral very specifically for each virus there's more and more antivirals coming up but still there's many diseases where we don't have any a disease that is disproportionately impacts regions like Western Pacific afca Africa and Southeast Asia but leaves no corner of the world untouched from its modes of transmission including mother to child and contact with infected fluids to the urgent need for accessible prevention and Innovative therapies this is a conversation about life death and the potential of change and how one can maybe break that immune tolerance and combat the infection that was what I found really fascinating joining us is

1:30 one of the most respected voices in the fight against Hepatitis B Professor Dr Protzer a Visionary virologist she's at the Forefront of research into the virus leading groundbreaking efforts to develop therapeutic vaccines and immune-based therapies that means we can try to optimize the vaccine designed to a way that we that we cure as many as possible but it will never be 100% but once you have the success then you can go on and improve in today's discussion is not just about understanding Hepatitis B it's about recognizing the urgency of global action and the stride science is making to fight this epidemic let's explore how Cutting Edge research

2:17 can turn the tide against one of the world's most pressing health challenges enjoy our [Music] conversation daily dose of honest science hello guys and welcome back to daily dose of Honor signs I'm your host Dr Chan Kumar and you're here of course for the best medical science podcast that you can hear on any podcast it is a true honor for me to introduce my guest today a globally respected virologist whose work has an extra extraordinary impact on the field of infectious diseases Professor Dr Protzer has dedicated her career to understanding and combating vir virus related diseases particularly viral hepatitis and more recently covid-19 her groundbreaking

3:06 contributions to science have not only Advanced our understanding of how virus is intact with the human body but also paved the way for Innovative immune therapies and vaccines as the Director of The Institute of virology at helmont's Munich and the Technical University of Munich Professor Protzer exemplifies leadership in research and collaborations besides her role as director she is also SP spokesperson for the translational unit hepatitis at the German Center for infection research she has also built networks that span disciplines and borders spearheading in in initiatives like the EU Consortium tavak B which is advancing a revolutionary therapeutic vaccine for Hepatitis B and a groundbreaking antibody and teasa based therapies for sasov

3:52 2 her academic journey is both inspiring inspiring and remarkable from earning her medical degree at the University of aangan to her pivotal postdoc work on Hepatitis B virus biology at the University of hiber she has consistently pushed the frontiers of virology her leadership continues to transform discoveries into the in the lab into the life-saving applications in the clinic benefiting patients worldwide Professor Protzer Excellence has been recognized with numerous prestigious Awards including the hins Maya liess medal in 2020 the dzif prize for translational research in 2021 and the Bavarian order of Merit in 2022 a dedication to interdisciplinary collaboration and her tireless efforts

4:41 to translate science into impactful therapies are a testament to her Visionary approach today we will dwell into her Incredible Journey her expertise in combating viral diseases and the future of immune therapies please a warm welcome to Professor Dr Ulrike Protzer thank you so much for making your time and joining us today and it's immense privilege for me um that yeah you're honoring me here as as a guest yeah thanks for very much for having me as a guest um from Professor we just dive directly into it because um we want to get to know you a bit more so um the first question that comes into my mind is how did you actually get into medicine and Science and what were like key points

5:29 in your life that you decided to go into that direction when I finished my high school diploma the abitur in Germany I was sort of torn in between studying biochemistry or studying medicine then I was lucky I immediately got a place to study medicine and I said okay I'll go there but I never lost the idea to do science and that's basically yeah which which really goes throughout my career oh awesome um so you're um specialized in Internal Medicine right and um specifically in viral infection so um why do you choose internal medicine and viral infection why is this so uh fascinating for you when I started doing medicine after f after finishing my University education I thought I want to do

6:19 something where I have a relatively broad education and then can really decide in which speciality to go and I did that and then I saw a lot of patients suffering from viral hepatitis and the mother of a very good colleague of mine she died of hepatitis B and there were many patients having hepatitis C so I got interested in that and I started reading about that in more detail and then I was we had the first therapies becoming available with the interference and we started doing that and we saw okay they have a lot of side effects and they have limited effects and that's what really brought my interest in developing a better treatment and a better cure for them so so you're seeing patients uh also with um this infection still or no not

7:05 anymore because um when I finished my training under my board exam for Internal Medicine then I went into real science so basic science I went to the center of molecular biology in heidleberg uh working with hey cheller at that time and he was the world known specialist on molecular biology of hepatitis B and I thought okay that's a very good education to really understand the virus and with that basis try to understand the virus host interaction and develop novel therapies and after I did a post talk for yeah a little more than three years three and a half years I thought maybe as a as an MD I should go back into medicine and then I chose uh the subject virology because I

7:51 thought that really brings Both Worlds together the scientific world and the medical world where I can yeah hopefully diagnose and also help people yeah wow um that's really cool um maybe um what kind of question do you think are still not answered in virology so um what is haunting you maybe even in nights many questions um so first of all unlike bacteria where you can use an antibiotic combating a lot of different bacteria viruses are different there is no broadly acting antivirals yet um so we have to develop an antiviral very specifically for each virus there's more and more antivirals coming up but still

8:37 there's many diseases where we don't have any take the very frequent epar virus infection which affects like 40% of the population and you can develop mononucleosis you can um develop or that even gives you a risk to develop multiple sclerosis and there is just no drug available there is no vaccine available and there is many of these examp examples for looking at the viral hepatitis we have a drug for Hepatitis C but we don't have a vaccine so numbers worldwide don't go down the other way around for Hepatitis B virus we have a prophylactic vaccine but we don't have a Curative therapy so still more and more people die yeah or also for HIV right so for HIV as well it's a disease where we

9:24 don't have a cure where we don't have a vaccine we can treat the disease and that gives you a relatively normal life but of course you would like to really prevent getting the infection or if you cannot prevent it cure it um on the note of that of course um when you have such a important role to fulfill I ask myself um how can you combine your career with your private life right it's very um taking a really big toall sometimes on you because um as we heard in the introduction you are also um a project called coordinator on a European level so um how do you balance Both Worlds and what kind of lessons did you learned throughout the years probably you need to be somewhat

10:12 organized and you need to be able to that's what a colleague told me very early in my career cut edges so for a time you focus on something and you don't focus on the other things and once you've done that or brought that part a step forward then you take the next next one and um of course you have to see how you can balance that also with family I have two kids and uh that luckily worked out very well because my husband is also a scientist so he always understood that I do not stop working at 6 o' but we do the family part together and once the kids are in bed then you start again sitting and writing and uh that that were both of us and we really shared I think that's an important point if you

10:59 if you want to have combined family and a demanding position and professional life then you have to share you have to share responsibilities between the two partners definitely and um may I ask uh what is your um husband doing in which field is he he's an immunologist he's also Professor also full profess so the perfect couple actually the perfect couple I understand the viruses he understands the immunology and we always fight about little things or um no no no more about does the immune system win or does the virus win ah okay um because imun uh Immunology is right now also um really at the Forefront because we have new um

11:47 therapies coming up where we boost the immune system with um or at least um this te car cell therapy right um where we take out from the patient the tea cells and not manipulate but um reprogram them in such a way that they can actually fight against a certain cancer type um so um is this also something that you're um seeing in your um field that um we can reprogram these to fight against viruses instead of cancer definitely definitely I mean immune therapies there was a huge advance in the last in the in the recent years I mean immune therapy has become sometimes the leading therapy for Cancers and te- cell therapy whether that's car te- cells or t- cells

12:37 redirected by t- cell receptors which are cloned doesn't really matter but that's a really promising approach and um also of course um checkpoint inhibition yeah and even the combination of both or so we always looked into the cancer field and thought we're working on a chronic infection Hepatitis B is a chronic infection which affects more than 250 million people a year yes and 1.1 million die of that disease every that's a lot that's a lot and as we don't have antivirs that can cure we thought we have to use the immune system so we looked into the cancer field and look what they are doing and then try to to learn from that and apply that for for also The Chronic viral infections and I think there is a grand a great opportunity and that's not only

13:26 restricted to the viral infection but these viruses also cause cancers yeah so you can even either prevent cancer that's the ideal situation when you cure the the infection or if you detect the cancer then in a stage where it still can be treated you can even use the virus targeted therapies to treat the cancer that's also what we are following yes yeah um but ideally you don't develop the disease in the first place right so you stop the virus actually replicating itself in the cells right um so we come to this part um in the very late stages um but maybe um I also saw that you're um someone who is collaborating a lot so what I wanted to know from you is um why do you think is

14:14 collaboration key in research or in today's research field and um what excites you the most when you do a collaboration I think when you're working in science you rapidly recognize that you cannot know everything you cannot be specialized in everything and you're not the brightest person in the world that was also something which I learned and I actually enjoy to learn because it gives you the opportunity to to say okay I ask a question that's my special knowhow but there is others around which are really excellent and they have specific knowhow how can we collaborate yeah how can we work together to push the knowhow forward to push the idea of Novel therapy

14:59 or to just push the understanding the scientific understanding forward and um I think that's really the fun part in science but um sometimes collaboration cannot be so easy right um so when you face problems um how do you usually um mitigate that or I think in collaboration it's like in a partnership it depends very much on whom you collaborate with and whom you choose as a partner and you should always be a little careful before initiating a collaboration or friendship and maybe talk to that person and very openly also talk about your expectations and ask the other person what's their expectations and once you have a common ground um then you can you can really

15:49 start the collaboration and then I never actually experienced bigger problems yeah so open communication is the key uh right at the beginning really openly exchange what's the expectation of the other person what how what willingness or how high is the willingness of the other party to contribute to your problem yeah and how much can you give away also of you know how just try to Define that at the beginning of a collaboration and then go ahead sometimes it also develops during collaborations and when you find out the collaboration doesn't work just stop it so there were some times where you said we need to stop now the collaboration because it's not leading where you want

16:34 to go yeah I mean most frequently the other party just doesn't deliver what you expect okay so that means um they have just other things to do they're more everybody's very busy and it's only only a question how you prioritize what you're doing and if you don't or your project doesn't get the priority you want it to have then maybe you have to look for somebody else that's not a bad thing to do no definitely not so um it's always good to know if someone else is doing similar things and uh maybe that one or that person has more capacity right now and can deliver maybe also new insights by novel approaches that maybe someone else didn't had right um so um of course um we met throughout a really

17:25 nice uh meeting and you were also talking about mentorship and uh that really set back in my brain so I just wanted to know from you um what makes a good Mentor in your opinion I think a good Mentor is somebody who demands your input not somebody who tells you what to do that's not mentorship that's more like a I don't know bossy uh person but a mentorship means that somebody encourages you to build on your own strength to expand based on your own strength what you're doing your Kno how and your projects and just gives you a little bit of guidance in the right direction and also challenges you so if somebody says well

18:13 now you're working on that project for two years but there is still no Real Results did you ever think about how that could come to an end um Everybody also has to learn as stupid as it as it sounds publish or perish so you have to finish project parts and you have to publish them because if it's only your private KN how other people cannot know it and it doesn't help anybody else it also doesn't help science and it doesn't help the the society so I think it's an obligation which we have to publish that or make it public and that's of course you should do that in a in a very solid way and that means planning and a good Mentor will help you to do that and um when you say we should um publish our

19:00 stuff um so are you a big advocate of um publishing small or rather the bigger picture not the 100,000 very small publication which nobody reads that doesn't help it's always better if you are able to publish a little bigger picture because then people will recognize this then people will read it and only if other people recognize it and read it um or listen to it if it's a podcast yeah then it will it will help them to in their understanding and it will advance the science yeah because right now I'm working on a project that is um kind of big so I'm doing all the C culture and um it's more based on a drug Discovery um lineage let's say um but I feel like I have a vision how this paper

19:48 should look like it should be a resource paper in the end because I cannot address every biology of this little sell lines um but I think um and you can give your stance on it most omix papers are actually um I guess the future because um more and more is published on protein level on DNA level so how do you stand on it that um multiomics are the way to go for future Publications multi omix is great to collect data but just collecting data without having an idea why you collect the data is useless yeah so you should always have a hypothesis which you want to address and then think about which is the right technology that may be very well be an an omix technology and may also be different

20:35 omix technology but it may also be very specific um experiments and so I think starting off from a question and from a clear hypothesis and then select what do I want to do that makes best use out of your data and and finally brings a success and all the omx data you will always have to confirm with specific experimentation yeah because uh you may have just a noise you may have a background signal yeah which you over interpret so you always have to confirm it and uh in your case do you also apply multiomic St uh multiomic uh platform uh technology to understand we apply omix and whether it's then multiomics

21:24 that really depends on the question oh okay so we do a lot of single cell RNA sequencing we apply proteomics uh we try to do spatial transcriptomics and even proteomics right now but which technology we apply really depends on the question we are asking MH okay very very interesting um the last question to this section would be um um what have been the biggest challenges in translating lab breakthroughs into the real world impact um specifically now on viral diseases there's a lot of challenges I mean we we always say there is a valley of death where most of the projects fall in because there is so many challenges the first challenge is

22:09 if you want to translate something into the clinics then you really have to think about what is the final goal what is the disease I want to treat and what is the clinical study setup where I can prove that my new drug or new treatment is better than what is already existing because that is at the end required then you think have to think about finances how can you produce how can you produce in an efficient way and in a high quality otherwise you'll never get there so there is a lot of challenges and I think um for me it helped a lot that I had the clinical experience because that made it very easy to talk to the clinicians and discuss about the the final goal the setup of a clinical trial and then you go back and you define the different steps which you need but there's a lot of steps so really transl in something from the lab

23:01 into a clinical trial not being a big pharmaceutical company is quite demanding and meets a big team which is really dedicated to doing that because it means you don't publish for a while yeah you you just work on the translational part and also um basic research is not always very straightforward right so sometimes it could be that the hypothesis you have it's not true it's a bit different and then you have to find ways to um continue and uh maybe follow the new path or maybe have a new hypothesis right so um that's also something uh people need to keep in mind that why it's so difficult to translate it later on in medicine because Mouse models if you have don't

23:49 translate all the time very well to what we see in the clinics right so it is a tool that we use but um of course it's not the ideal one it is a very good tool I think actually if you design your models right and if you control your models if you design your models to show what you want to see then of course it's not necessarily true but if you take a model which is unbiased at the beginning and then you see something uh then that's a very good predictor and a lot a lot of the therapies which are in the clinics and which are approved now were developed and also even discovered in Mouse models yeah the very very interesting and also um we come to

24:35 that part a bit later but I would have a question how to design such models right um but I would like to conclude this part um and I would want to thank you for sharing your passion and insights how you got into medicine and science of course and um how you become actually the frontier in these fields um now I would like to go a bit more into your research focus and before that I would like to give the audience the opportunity to understand viral disease infections and research a bit more so um because it's kind of interesting and important to know how does this work and uh later on also for the later part um how your therapeutic vaccine for chronic Hepatitis B actually functions um it's

25:21 important to catch the audience on important Basics to understand the complex world of viruses and how they infect us so I would like like to know from you um please explain us a bit of course I know what a virus is but still the people should know what is a virus um was it made of and um how do we CL classify them um I think after the pandemic with covid um people are still interested to know oh definitely I mean since um covid-19 we have 50 Millions virologists not soccer trainers but virologists but um I think it's really important to understand what viruses a virus is basically uh a gene transfer vehicle if you want to see that so a virus has a genetic information that can be RNA

26:10 or DNA it just needs to find way to replicate it whatever it is and that genetic information that Genome of the virus needs to be transported it needs to be transported into a new cell because there it has to replicate and it has to leave the cell again that's why the viruses form particles and the particles usually consist out of a capset that's proteins which cover and protect the genome and then sometimes viruses have envelopes why because if you want to leave a cell there's always a membrane on on the top of the cell yeah and if the virus takes a part of the membrane with it then it's an envelope virus and it can leave the cell without destroying the cell immediately

26:57 and also for going into a cell the envelope the membrane is helpful uh because that can simply fuse with a new cell mediated by varus proteins integrated into that into that um envelope or membraneous part of the en envelope so that's what a virus consists of a genome a capsid which is a protein covering the genome and then a membranous envelope where virus proteins are are integrated into and then we decide between double strand RNA double strand uh DNA right different forms single stranded double stranded RNA DNA uh even viruses which need both for both for replication

27:43 like HIV or the Hepatitis B virus so reverse transcription viruses um but I think that's already than very specific now the question is um how do we classify them so usually we just say it's enveloped or non- enveloped and we say it contains RNA and DNA why do we do that because for Diagnostic purposes you need to know whether you look for RNA or for DNA for RNA you have to do a reverse transcription step and produce cdna before whereas for DNA you can right away do a PCC and the PCR is just the gold standard to detect a virus mhm and uh usually the PCR is with standard primers that always recognizes a specific piece in the DNA yes um so you usually have primary

28:30 sets you have more than one primary set because you only say it's really you really detect a virus when you detect at least two parts within the viral genome and um they are designed to be independent of virus variations which naturally exist viruses undergo Evolution very quick and they can vary their genomes because their polymerases they make mistakes mhm and then it's just a a random thing with mutation comes up and a new variant if that has then advantage in replication or infection then we call it a new variant and of course if you do a Diagnostics you should detect all of these variants yes so you very carefully have to select and then also validate your primary set what you use this rapid

29:19 Evolution we also saw by Corona so we had in the beginning let's say the mother strain and then in the end it evolved to this uh I think the last one was Omicron I guess um but of course um that is throughout I think several months it was right years actually even yeah okay yeah I mean SAR Corona viruses actually that sounds maybe strange are slowly evolving viruses they're very stable why because when they replicate their genome they have an enzyme which does proof reading like we have when our cells divide our DNA polymerase they also do proofreading so not to make mistakes in every new cell and create cancers all the time and the same thing s Corona viruses have included but still

30:08 because they replicated such high levels even if the if the um rate of mistakes is something like 10 up to the minus 8 10 up to Theus 12 you find them and if they have an evolutionary Advantage then you will see them as a new population as a new viral variant could that evolutionary advantages be it could either be it replicates to higher levels so it produces more progeny and can infect easier infect other people it can be more infectious that usually means the entry into a new cell is more efficient or the virus is more stable against environmental challenges because um it doesn't help the virus if it just spreads in your own body it has to get from one individual to the next

30:55 individual so usually the viruses do do that by causing symptoms MH so when you sneeze or when you cuff or when you have a diarrhea or you wmit that's the way of viruses to to induce Sy symptoms and then infect the the next individual um that's how they do it and depending on um how they replicate how infectious a single particle is and how well they spread why are these symptoms and how stable they are in the environment that determines their evolutionary advantage and whether you will see them or you won't see them at the end and that's very nice because I mean with sou coronav virus we could really study Evolution yeah in Vivo or in real life right yeah in real life and uh um it's

31:44 some part very fascinating to see um how this uh Corona virus evolved and uh infected all of us uh at some point and um I was also remarkably uh astonished about um how quick we actually found a vaccine against it right so um that was also really impressive but of course you're also now working on um postco as well and um how the Corona virus um infects um or it has been shown in numerous studies that um the Corona virus persists and uh causes lung damages or heart damages so um we are still not done with the research so we are just at the beginning and you one of the Frontiers because we need therapies

32:30 actually for all the people who are suffering from it yeah definitely and maybe I should add one point in evolution people were always afraid that the killer virus comes up and I always told them it's unlikely why is that unlikely because if the virus causes initially a very severe disease you don't run around and spread the virus yeah you go back home and lay in your bed and then you have very few contacts so for a virus it's not an Evol evolutionary advantage to cause disease is a disadvantage to cause disease yeah I think that's something to really understand and I kept on telling that to politicians and others who were very afraid of the killer virus that it's very very unlikely that evolutionary this comes up the evolution will always

33:16 go toward its being more infectious but Le less pathogenic still you mentioned long covid um of course there may be long-term consequences which the virus does doesn't care about because it's already been spread by the infected individual to the next individual so the virus population don't doesn't care about long covid yeah but of course the individuals care about it and there is really people who suffer a lot from from long-term consequences it's not necessarily A Persistence of the virus we really tried very hard to find that it's somehow proteins M which may persist in very um immun privileged niches but usually the long Co symptoms or the the long-term symptoms are also consequences

34:03 of the immune response we have because uh the immune response can help to eliminate the virus but it can also cause damage and if it's overreacting if it's overreactive or I mean if it just is reactive in the right way but there is a lot of cells infected in a lung or in a liver for example and the immune system has to kill most of those then of course that causes a damage yeah definitely yeah and um we are still in our infancies to understand what postco actually means um and there's a lot of research right now ongoing um also there were some studies um found that virus particles were found in the brain of some patients or causing maybe some neurological problems but this is all

34:51 still um very you know in infancies and we cannot really say something about it just um that it was a good for everyone who does or did the vaccination it was a good thing to do um not getting it does also me not getting the consequences know yeah and uh because it's also something um because vaccines as um as we know saved million of lives right but the problem is that we still have the skepticism yet there are people who are antivaccine right and um maybe do you have an answer why we why these people still have mistrust in for instance vaccines I think there is very different reasons so when you look at vaccines overall they saved the most lives of all Medical

35:43 Treatments we have many more than of treating uh hypertension or uh preventing heart infar more than antibiotics that vaccines were throughout the years the most most successful means and preventing disease and preventing death and even if you cannot prevent an infection like with the Corona virus vaccine that we learned it doesn't give you sterilizing immunity you still can be infected but you don't fall severely ill anymore you don't have to go to the hospital and you don't die and I think that's the really important thing about it so really the prevention of diseases now why are people skeptic um that's a little hard to say I think there are people who are skeptic and who

36:31 want to understand what's the advantage and what's also potential side effects and I think that's very fair yeah and we have to be very open yeah nothing which we do is 100% safe even if we try to design vaccines to be 99.99 something safe but it's never 100% And um then you also have to understand what could be the side effects it could be either immediate reactogenicity that means after vaccination you don't feel very well you um may even develop a fever for one or two days that's a sign that your immune system reacts and that's basically what you want because you need a fit immune system to to defeat off the virus and even if you catch it to get it out of your body as as fast as you can and prevent that it goes into nerves or

37:20 brains or whatever um then there is also severe side effects of vaccines but there they're really rare they're really really rare the long goinging consequences they the the numbers are by three log which means a thousand to a million fold lower than the consequences of an infection and that's also important to understand you also have to see what do you prevent which potential consequences of an infection do you prevent versus which is the risk you take and of course it's it's really bad if you are the person who had the risk and suffers from from the remaining very

38:05 small risk of a vaccine and and there we need to care for those people that's no question but the overall population and the society really um yeah there was a lot of life saved I mean there is um the economists sometime once tried to measure that and they said there is about 30 probably yeah between 177 and um or 15 and 30 Million Lives saved by the vaccines which is a lot yeah which is really a lot if you see um how many uh people died in the beginning right and then if you see later on um how many actually survived and only had mild infections even if um so that was really incredible to see I can tell you my own

38:53 experience I was in the expert group of the hospital and we meeting every morning MH and in the phase where we had the Delta virus infection so end of um 2020 yeah um we had every morning like there were there were 10 new people coming to the hospital who had to go onto intensity care war and we were asking how did you manage where did you get the breads from and they said well another Aid died overnight yeah and it was every morning and then we had the vaccine coming and that really dropped dramatically wow that was that was very very impressive to experience that and I think everybody working in the hospital had the same um the same experience at that time and that really made um the

39:40 the infection to something we could sort of handle that make made the infections to not a nice thing but it's just there we cannot get rid of the virus but a virus we can live with and also for the hospital people making it easier to handle the patients that need urgent care because um you don't need to take care anymore of the people who are vaccinated in that sense right because they don't develop these severe conditions anymore um so that was also a big thing and um I still have a lot of um respect for the people who worked at the Forefront it was just uh insane yeah they did it in incredible yeah incredible amount of work particularly those who care for the patients

40:27 whether that's the caretakers or that's the doctors um we really have to respect what they have done so um but also I mean there is a lot of other severe diseases it's not only covid there were heart infections there were Strokes there were a lot of other a lot of cancers and we couldn't care for those patients as we usually can because of the huge amount of patients coming in so it was really necessary to release the workforce again for those other diseases which also needed attention or people who needed a treatment for their cancer right that was also kind of on the hold and uh it's also not really good if you have to stop your chemotherapy in the middle of uh um your fifth uh maybe

41:16 injection or so it's also not really um good because it could remission then and then how do you fight against that specific type that has been now resistance against the chemo so it was very hard to find the balance particularly in the hospitals between treating the covid patients but also taking care of all the others which needed the care um I would like to move on on um because we would like to talk about your very recent um amazing um first clinical trial that you started um so that people understand why Hepatitis B is so let's say um dangerous um um so I would like to know from you what distinguishes this virus from others

42:03 so what makes it so special and why did you have you dedicated the research on this subject on especially the virus that causes hepatitis B because in my early times in the clinics I really saw patients dying from that disease that causes liver curosis that causes liver cancer and there was just nothing you could do for them anymore and then I had the opportunity when I still even worked in the clinics to work on the on the virus to to analyze patient samples in very much detail by sequencing methods available at that time and also other methods to characterize the immune response to characterize viral variance and that's how I basically got into that topic and got interested and with that basic then I could um start my own group and start develop something where I

42:53 believed it could be a cure and could be a help and I always was convinced antivirals will probably not do it because like for HIV there is a persistence form and the nucleus of an infected cell and it's almost impossible to Target with an antiviral that's why I thought we need an immune therapy we need something which stimulates the immune response because we know that that can combat the virus we know that there is very rare cases like 0.5% but those can get rid of a chronic infection and can cure it so we always thought okay we have to find ways how to specifically stimulate that type of an immunity in the chronically infected and that's what drove all the research and what makes the virus so special so um compared to other

43:41 viruses that is so well adapted basically it's adapted to infect an individual usually around birth then live with this individual for 35 years until even they have had their kids and um um transmitted on the virus very often to the kids and then causes disease and causes death and uh understanding that and trying to to understand how one can maybe break that immune tolerance and combat the infection that was what I found really fascinating part of it because um usually um Hepatitis B is then diagnosed the chronic condition I mean in elderly people or also in young if you look for

44:32 that you will also diagnose it in young people but most people don't look for it I always say it's the most frequent neglected disease in the world because now now just one and a half years ago we convinced the German government that you're allowed to test for the virus once you're 35 wow okay it's relatively late but you're allowed to do one test in your routine screening uh but still no knowing that even in Germany we have about 0.5% so every 200th person is infected most of them just don't know it so they can also not trade it they can't do anything against it and worldwide it's even more yeah um that means we really have to push diagnosis we of course have to put push preventive vaccination so to

45:20 prevent that people get it but we also have to care for those who already carry the virus and carry it decades very often um maybe on the symptoms that people develop um during their life so um how does the infection actually affect the body we talked about liver curosis and liver cancer but um what are maybe other symptoms or side effects that this virus brings with it it's really the liver disease and the liver disease has symptoms it causes you to be tired it causes um the the that at the end when the liver doesn't function anymore but that means it's already 90% destroyed that um the heem cannot be degraded properly and transported out of the body that's why you get then yellow eyes or

46:08 yellow skin because the U that's the the color of the which usually the the remaining stuff from heem degradation which usually should be transported out yeah via uh the liver and the and the gallbladder um and the function of the liver is to synthesize proteins and to detoxify your body and also these functions cannot then be properly done anymore so your blood clotting go goes down you have an increased risk to to uh bleed you have and you develop Cancers and that's probably the most deadly thing how about um liver transplant sometimes so would that work for some people or is this also something that is not the problem is that was tried but which the virus

46:58 persists somewhere it's highly infectious one virus particle is probably enough to infect at least it's enough to infect a chimpanzee so probably it's also enough to infect a human okay and that's the likelihood that this one virus particle remains somewhere in your blood and rapidly infects your new liver is very high and that's why for a long time Hepatitis B was excluded from liver transplantation nowadays we have means to try to prevent the infection but it's still really done um then of course we would like to um see how is The Clinical Laboratory uh measurements to so you said there's a screening um so usually you do just a PCR or how does the actual um even

47:47 easier you can simply do a serology test you test for as antigen and if as antigen is there that means you carry the virus and then you can look deeper into it is it an active infection how high is your virus replication how high is your risk and so onh but the the initial detection is a very simple and also cheap essay so it can even be done as a bedside test and it costs less than a Euro or less than a dollar and how does it um be different from the um so when you do the vaccination you also develop antibodies against it right can we do the difference between it's very easy to distinguish because when you develop antibodies you develop antihbs antibodies whereas if you detect the

48:32 virus you detect the viral antigen the virus has the specificity that it secretes a lot of empty envelopes into the blood and that's what we can measure at HPS antigen that's really easy to detect and um of course when we talk about um The Chronic Hepatitis B in patients then uh we would also like to know um uh so there are antiviral therapies against it but uh now it comes uh to you um why did you had the urge to actually get this new therapy ongoing that you developed because as I said antivirs don't do the job people always hoped they would do it and pharmaceutical companies jumped into that with a with a

49:20 success of developing antivirals for Hepatitis C they jumped onto that they developed new antivirals and they found what actually we already expected that they will not cure the disease um and then we always said okay we need a stimulation of the immune system and then the question is how can you best do that and a therapeutic vaccine is different from a prophylactic vaccine prophylactic vaccine mainly stimulates antibody responses to prevent a virus to go in but also some tea cells once it's in that it cannot spread and cause disease a therapeutic vaccine is different because you need mainly a t- cell response to really Target the cells which carry the virus eliminate them also

50:05 carry just virus remnants and may develop into cancer cells that's the secondary um effect which you had really prevent the the cancer and this needs a specific design so we worked for many years now on the best design of such a therapeutic vaccine M um so I would like to come to this therapeutic vaccine um because for me it's a groundbreaking concept and um so what I would like to know and we learned now in the section what the immune system and the viral response is so um you worked on this after 12 years doing this preclinical research so a lot of time and uh sweat have gone into it and um I want to congratulate you because uh January 25th this year actually um you have uh initiated

50:56 the first clinical trial phase right for your um um the treating chronic Hepatitis B by this therapeutic vacine and um um so this is uh kind of like really interesting to know what is like the difference now to the as you said to the um uh to the normal vaccines that we have so what do you specifically found out to actually fight against Hepatitis B in the chronic condition yeah so the first thing is we needed a model to develop the vaccine so the first thing we did is we developed a mouse model which allowed us to have a persistent infection a carrier State very similar to what we have in patients

51:45 and then we could vaccinate the mice and see test do they eliminate the virus yes or no and um once we had that we could test different vaccine platforms and we found out that combining a virus like particle vaccine so that's a protein based vaccine very classical together with a Vectra based vaccine gives the best type of immunity we need to really combat the virus and this what we call a heterologous prime boost you because you don't use the same thing for priming and for boosting the immune system but you use different means so a protein first and then a varo vector and that's what then we once we had it and we had good preclinical results we could convince the funders

52:31 that they give us money to develop that into the clinics this was in 2017 18 relatively before Co started because that then also caused some complications else for to bring something into the clinics and our vaccine is completely publicly funded so far it's no company behind that um when you want to bring that into the clinic of course you need somebody who has a GMP lab and can produce that for you that's a very demanding process as you have to do all the quality controls but now Corona came and all the GMP facilities they produced Corona vaccines and we were there standing with our small project relative to the Big Corona vaccination projects and they said well it's not really interesting for us so luckily we had build up very good

53:21 collaborations with some of them so they still sort of brought our projects forward okay and we were ready to go in 2023 once you have that then you can apply for a clinical trial or write a clinical trial protocol hand in all the quality data which is a huge it's like 900 Pages you have to hand in okay to the regulatories then they test all this they send it back to you say okay you need some more data and this and that and that then you revise you send back and then you get approval of your protocol wow so and once you have that then you have to have a study site who's ready to go and is able to do that because these like first in man very early clinical trials um they need specific established situations you need

54:10 to be able to take care of something would happen to do a lot of um Testing Lab testings and so on so we found one luckily with Partners here in Munich and uh we could start the trial and now it's running so healthy volunteers have been vaccinated we the results are not out yet but so far it looks as if the vaccine is safe that's the most important thing and it's also immunogenic and now we're really eagerly waiting for the results and we handed in a second study protocol that's for testing the first patients then to also see whether the the vaccine would really be able to combat the virus yeah and that has also been granted and will hopefully start very soon mhm so um did you follow a bit like biontech is uh did

54:58 it with its mRNA vaccines back then so that you have the first clinical trial but also the second clinical trial um coming up because there was a huge discussion that we maybe should um think of making clinical trials a bit more quicker so that um therapies are more quicker available so I just wanted to know if you followed the same principle or similar yes and I must say the regulatory authorities are very helpful in Germany it's not that you always say say they they restrict you that was not our experience because what we told them is that we we test the first scheme in healthy individuals and then we right away can go into patients they accepted that that's why the first trial in the healthy volunteers is still running but the the setup which we have proven

55:44 to be safe in that population of healthy individuals we're now allowed to already take into chronically infected patients and once we have the next setup tested we can take that over and of course speeds up the the whole development process a lot um so uh when the second trial is very successful um the third trial which is a larger patient cohort will be initiated so um can you give us like a prospect of how many years we have to wait till this therapy might be available so first of all this is very costly U this is why developing vaccines is also not really interesting for pharmac IAL companies anymore so now you need until to have a first trial in patients you need about 20 million Euro

56:35 dollars um and then to go into the bigger population this is probably rather about 150 million this you will not be able to fund with Public Funding anymore so what we have to do is we have to now prove that it safe and that it's somehow efficacious and then we have to see whether we can partner with a bigger pharmaceutical company or a public private partnership or something which brings us the the essential funding to even go on and it's very hard to predict how long that would take but we first have to do these first steps now and when we once we see that is successful then we can go out and seek the funding for the next stage and and do it so usually the clinical the first and second clinical trial takes roughly 5

57:24 years I guess right around yeah around so um maybe maybe a little less maybe 3 to four years and then the next stage is about 2 to 3 years so if it's already promising you could actually reach out to I don't know biotech fizer and so on and sell kind of your uh new vaccination of course um but um what I would like to know is um you worked in Mouse models and you figured that out um of course people are starting now to move away a bit from Mouse models um as we had a short discussion about how translatable it is to human um I would just wanted to know did you work on organoids or any other Advanced uh cell culture models

58:10 to see if it's effective um for your um therapy the problem with vaccines is you can't because you cannot induce immunity in an organoid I can generate immune cells artificially and put them onto an organoid and ask the question what do the immune cells do that works but I cannot induce immunity so in principle for vaccine development we are still not there still not there that we have alternative method so the only thing if you want to avoid animal models would be to right away go into humans but that's not a good idea I think we have to really test safety very strictly before and also efficacy yeah if you don't see that your your vaccine is immunogenic and IND uses really the type of immune

58:57 response you need you would not go into humans it's much too costly and also it's it doesn't make sense it's ethically not not justified so I think we still need those preclinical models but as we discussed at the beginning they should not be designed to get the results you want to have yes they should be designed to to be really preclinical and meaning that they can give a yes or no answer so it could also be a bad news which you get out of this models that's the important thing so really to choose the right ones um can you maybe just quickly elaborate how do you design such a model so what exactly what I said um that should mimic the human situation in our case it

59:46 should be a model which tolerates the virus replication without clearing Theus a mouse strain or no it's the way how you bring the virus in in our case ah okay and the the good thing is the mice don't even feel feel um unhappy or unwell they're perfectly well they stay alive as long as a normal Mouse does because in mice it doesn't cause the liver disease which it causes in humans that's for the mice that's the good thing but they still allow us to to test when we now vaccinate the mouse whether the immune system will clear the virus yes or no and um we also had answers which is good because that means we have a model which gives us the correct idea it's still not a human of course but I

1:00:34 think if you use good models then you get a very valid answer to to your question and that's an important point an important step in and um when you uh compared your results now um in the mouse model I was uh interested in um you said you the clearance rate was kind of high um but would you say there is still like I don't know 1% could be still the virus is not fight off so um how these maybe 1% might have an impact on remission do you know something about this yes it's not that we cure all the mice which is also again a good sign that it's not a biased model so there is always a certain percentage which we cannot

1:01:20 cure and um that will be the same situation in the patients later on that means we can try to optimize the vaccine design to a way that we that we cure as many as possible but it will never be 100% but once you have the success then you can go on and improve and and try to find a way when you look at how hepatitis C therapies for example came up we started off with a cure rate of 30 40% And Then There came improvements that went up to 60% it came new improvements and went up to 80% and now we are at 99.9% cure but it was over the years steady improvements of the therapies and I think that's that's also what we have to do here yes yeah um so that's like the initial vaccine that can

1:02:08 be further improved to even uh help more and maybe also understanding in the human um how maybe the vaccine works because in a mouse model you will never know how it actually translate into human and that will also give you data to work on and make a better vaccine maybe 2.0 or something like this and that's the big big Advantage if you do a study out in the academic context also that's very rare I've learned in Germany that's really the exception but it gives us the the opportunity to really study all the immune responses in the vaccinated individuals in very very much details Farm companies usually don't do that because they're not interested they just want to get as fast as possible to

1:02:54 some end points but I think it's so important to do that and understand what is the good things and what's maybe also the limitations um that's a lot of work but we have a very active team working only specifically of that part of human Immunology to really understand how the vaccine Works in detail that is really amazing and fascinating for me um maybe on the note of this um what is maybe the future outlook of your um Consortium terak B so what are the maybe next steps or what you would like to Envision so once we've initiated the study of course all of us hope that we will have a cure maybe not in 100% but we said at least we want to have 30% everything more than the

1:03:40 30% would make us very very happy uh yeah and once we've done that then we have to think about how we can initiate the next bigger studies Sal we discussed that would again mean thinking about financing sources do we think it should be should go to a pharmaceutical company which probably would give a product coming out of a higher price or do we think we we should try to push a private public partnership and bringing that to the people in need in Africa in the different Asian countries that's a way that has not been decided yet no but to be able to decide that we first have to show that it works the yeah so we need the data and is safe right um so maybe

1:04:26 to conclude this little um uh summary here and also our little conversation maybe you can give us um a bit of an Insight uh about your future projects or any publication that are close to um you would like to share what is coming out of your lab maybe so what we're very much interested in at the moment is really the function of the T cells which we induce and why do they function and why do some of those tea cells not function as we want them to and we apply as we said omx Technologies to do that so we also needed to expand the team with people knowing about the bioinformatics we have to work together with bioinformaticians and um well that's I think the next things the next big steps

1:05:14 that will come out in parallel to still working on the molecular virology and more the basic aspects which we also push okay awesome then we can um maybe have some Publications on that um and one last question I would have before we conclude um if you could address one myth or Miss understanding about vaccines or viral diseases what would it be some people say Okay viruses do not cause disease they infect you but that's not severe it's just not true uh that was mis understanding um and a misinterpretation which we had for many years I think Co told us that it's not true now almost everybody understood

1:06:00 that point uh and K also showed What potent potential vaccines have but it also showed what problems vaccine development can bring and that's a societal problem we have to sort of deal with if you have people who do not go for numbers as we as scientists do and say okay the disadvantage is five cases and the advantage is 500,000 cases um many people don't understand this these numbers so we also have to do I think a lot of open discussion with people who are open to discuss there is some vacine vaccine uh antivaccine vaccinal that

1:06:46 don't want to discuss anymore okay then you can't do anything yeah but as long as people are open for discussion are open for getting information we have have to discuss with them we have to try to convince them by using numbers and um yeah it would be great if also in our general education um the feeling for numbers could maybe improved because that's what causes a lot of problems I think in our world and of course giving the right information to the public right so explaining things and uh make it more accessible for them um of course not breaking it too much down um still having a bit of complexity but this is also part why I'm doing this because I want that the people

1:07:32 understand and uh maybe that we may some people get back from the antivaccine and tell okay vaccines are okay or overall sign skepticism and fact skepticism and that we we help people to understand what it's correct facts and what it's false facts or fake facts yes yeah truly which is unfortunately on social media very propagated um and that's why it's important to have experts in the field that talk about it um so I completely agree and uh I'm really happy that you're sharing your results here and uh telling the people what you're working on and why this is important and also explaining a bit so the mechanism behind

1:08:18 it because for me I've been exposed to it so in theory I could read up again but many people just you know my parents they are not exposed to it and of course it's good to tell them why is this important and uh I really find um value in that that people tell okay that's a good thing to do and um there's signs backed up behind it and and we're not making any magic cure but it's really like something that we come up with novelty um so I would like to come to an end with this conversation and um I would like to thank you again for um explaining us how your therapy works now and um that it might in some years

1:09:06 help patient with chronic hepatitis B infection to actually yeah reduce the virus um um virus uh last so load load sorry um in in the liver and therefore maybe you know reduce the risk of getting curosis or liver cancer any type of this um yeah and uh dear listeners we come to an end and um yeah Professor Protzer if you would like to um I always have a little slogan uh at the end um but before that I would like to thank you from the bottom of my heart for the time in incredible research work on host virus interaction and um Zas 2 and

1:09:51 hepatitis B and um yeah I think I'm not exaggerating when I say I'm truly grateful and honored to have you here and talk about um yeah your over 20 years in experience and it deeply fills me with joint shows me how important the research in this field of virology is and especially having such you know pandemic behind it um and it illustrates the urge of Novel therapies and basic research um yeah if you enjoyed the conversation then please make sure to like it and if you want to see more episodes with future medical profession and scientist don't forget to follow And subscribe and um Professor Protzer if you agree I would like to say the slogan with you together okay so uh let's start one two

1:10:39 three let a little do of honest signs in your life and brighten up your day thank you very much see you [Music] guys daily dose of honest science a [Music]