Vaccines against viruses - protection against diseases

00:00:00: Summer is coming soon. Smile, it's time for your holiday. But when was the last time you

00:00:13: checked whether all your vaccinations are up to date and whether you have all your vaccinations

00:00:19: for your upcoming trip? Because depending on where you are traveling to, there are different

00:00:25: viruses on the move, some of which can cause life-threatening illnesses, either through

00:00:31: contaminated water or food, or through insects that can transmit them when they bite. They

00:00:38: can spread around the world due to climate change, traveling and global transport chains.

00:00:44: We have all experienced what this can mean in recent years. What can help? Vaccines

00:00:50: and other medicines that help our immune system to fight off these pathogens, but finding them

00:00:56: is not so easy. For Professor Thomas Peachman, head of the Institute of Experimental Virology at

00:01:03: Twincore and spokesperson for the Infection Research Research Program at the HCI, this means

00:01:10: "Challenge accepted". Today we talk about viruses, how important vaccines are, how difficult the

00:01:18: search for them is and how important interdisciplinarity is here.

00:01:21: How do bacteria and viruses trigger diseases? How does our immune system defend itself against

00:01:37: them and what must active substances be able to do to fight dangerous infections?

00:01:43: The Helmholtz Center for Infection Research is looking for answers to these questions.

00:01:49: How this research works, how the results are used in medicine and who the people are that do the

00:01:55: work. This you can listen to here at "Infect", the podcast of the Helmholtz Center for Infection

00:02:03: Research. I'm here in Hannover with the experimental virologist, Professor Thomas Peachman. Hi.

00:02:11: Hi Julia, nice to meet you. You do research in experimental virology at Twincore in Hannover.

00:02:17: This is a research facility for clinical and experimental infection research run by the

00:02:25: Hannover Medical School and the HCI. What exactly are you researching here?

00:02:30: Maybe I start with the name of our institute, Twincore. It means a twin of two cores. That means

00:02:37: on one part the medical school Hannover and the affiliation with the medical school,

00:02:41: the interaction with clinician scientists that is supposed to happen at Twincore.

00:02:46: The other part of the coin, the other core is the Helmholtz Center Infection Research,

00:02:50: which is the basic scientists, the natural scientists, the computer scientists. These

00:02:57: people like me that like to interact with physician scientists to solve medically related,

00:03:04: clinically related infectious disease problems and limitations and to do research that addresses

00:03:11: this type of questions towards solutions. In my case, that is work with viruses, hepatitis C virus,

00:03:17: a liver tropic virus and respiratory sensational virus RSV, a pathogen of the lung. These are

00:03:24: the two main pathogens I investigate. The RSV virus is a very current topic. Actually,

00:03:30: there was a new vaccine. It was a bit tricky, the research of the vaccine.

00:03:36: Yes. It has been a very long way and path to develop and ultimately license safe vaccines

00:03:43: against RSV. And all this development goes back into the 1950s when first attempts after the virus

00:03:50: had been discovered and its clinical relevance was recognized. So first attempts to develop a

00:03:56: vaccine failed actually in the clinical trials those days. Unfortunately, the children that were

00:04:01: vaccinated had a more severe cause of infection after the next exposure to the true virus. So

00:04:07: this vaccine had to be terminated. And that was a major setback for, I should say decades until

00:04:14: the field understood what was the reason behind that. How could we overcome this? And if you

00:04:20: look at it now after more than 50 years, it's a major success story because we were able to

00:04:26: overcome this and develop a safe vaccine, which is based on a fusion protein, the surface protein

00:04:33: of the virus, not in its natural form, but in an engineered form. So that means that after knowing

00:04:39: the structure of the protein, people in the United States were able to discover that they could

00:04:44: design an optimized antigen, which is better as an immunogen and safer than the natural antigen

00:04:50: of the virus itself. So that's a major achievement and that resulted in the licensing of these vaccines,

00:04:56: which we now have to protect the elderly, or which can be given to mothers to protect their

00:05:03: newborn children with antibodies that the mothers then donate to the newborn children.

00:05:07: A really great success. You also mentioned hepatitis C virus and this, yeah, you researched

00:05:16: for a very long time this virus. What was the most exciting thing about it for you?

00:05:22: Well, the most exciting thing for, if you look at the whole of HGV research is

00:05:28: the discovery of the virus itself in 1989. This was honored with a Nobel Prize to three colleagues

00:05:37: of mine, major achievement. And of course, once you know the virus, you could imagine,

00:05:42: well, the first thing that happened was you knew the virus, you could make save the blood supply

00:05:46: because at this time already, we were transplanting organs, we were giving blood donations to people

00:05:51: and we were transmitting the virus because we didn't know it was there. After that was there,

00:05:56: you could develop a diagnostic test to prevent this type of transmission. That was a huge breakthrough.

00:06:02: So that was the first and the second major things, of course, that enabled the discovery of

00:06:07: inhibitors of the virus and their development towards the clinic and now combination therapies

00:06:13: to treat this virus are available and can be used and are used worldwide to treat chronically

00:06:19: infected HGV patients. Hepatitis always seems very far away from us. Many people may relate it to

00:06:30: drug addicts or maybe sex workers. Why is it relevant for all of us?

00:06:36: Yeah, maybe I start first by saying there's different types of hepatitis viruses that are

00:06:41: quite different in biology and importantly, also in the mode and way of transmission,

00:06:46: how you can actually be infected. There's for instance, hepatitis A or E viruses,

00:06:52: which are much more easily transmitted than hepatitis C because you can ingest them by

00:06:58: contaminated food. We say fecal oral way of transmission or in terms of hepatitis E,

00:07:05: poorly baked or cooked meat, for instance, is a way of transmission. Whereas hepatitis C is a

00:07:12: bloodborne virus. That means whenever you have direct blood contact by this or that sort, needle

00:07:18: sharing one, but also sexual intercourse, depending on procedures, of course, is a way of transmission

00:07:25: and something where you can be infected. So what makes hepatitis C so dangerous for us and

00:07:32: why does the infection go unnoticed for so long? Once in contact with the virus, the virus homes

00:07:39: to the liver infects liver cells, but it's not such that the symptoms that you have after such a

00:07:44: primary infection are very specific. So you may feel fatigued, tired, just worn out. But it's not

00:07:52: such that you would have a calf or a running nose so that you would directly say, "Oh, I have something

00:07:57: going on in the lung." So you cannot pinpoint it. And you don't necessarily pinpoint it to a

00:08:03: transmission event because you're not next door neighbor in the train to somebody coughing at

00:08:07: you all the time. That's not the mode of transmission. So you cannot pinpoint it to a certain event.

00:08:11: And this combined, unspecific symptoms, not clear when there was a transmission event,

00:08:16: makes it likely possibility that you don't spot the transmission, don't realize. And then

00:08:24: this ongoing replication of the virus doesn't go unnoticed. There's a continuous immune response

00:08:29: towards the liver. Liver cells die, are eliminated. And that is something, if you

00:08:35: declinate that over decades and years, that causes liver disease and that accumulates,

00:08:39: and that is then something that you feel and better earlier than later.

00:08:44: because then you can treat it. That's the danger that it's kind of a hidden infection. You don't

00:08:49: realize it immediately. So there's a treatment now, but there is no vaccination. So why is it so

00:09:01: difficult to... Yeah, that's an important point. So some viruses, it's relatively easy to vaccinate.

00:09:08: That means what I mean with easy is that you don't have to engineer much. You don't have to

00:09:13: change the properties of the viral antigens in ways that they're more immunogenic. But you can use

00:09:19: them as a subunit vaccine, inject them and get a very strong immune response that is protective.

00:09:24: That can work in some viruses, but particularly for hepatitis C and also HIV, which are viruses

00:09:33: that cause chronic infection. That means they have learned or evolved, I should say,

00:09:39: to cope with strong immune responses. They have found ways and adapted towards evading the immune

00:09:46: system, avoiding immune responses, or being able to replicate despite of immune responses.

00:09:52: And that's a big challenge to vaccinate against such viruses and to understand the mechanism of

00:09:58: immune evasion and to engineer antigens and vaccines that overcome these endogenous adaptations

00:10:06: of the viruses. What I find very exciting is your research is on one hand very basic. I don't mean

00:10:15: simple, but small scale. And on the other hand, it's also very close to clinical application or to

00:10:23: humans. Is that what you mean by translational research? I should say people have very different

00:10:31: opinions on what exactly is translational research. Some people, and I understand the point of view,

00:10:37: say or define it very narrowly. Translational research is the type of research that transfers

00:10:47: basic science information towards an application in that sense. That is, for instance, for a

00:10:52: compound, the proof of concept, the compound works in an animal model. The toxicity studies,

00:10:59: that the compound is not toxic in a living organism. All the pharmacokinetic, pharmacodynamic

00:11:06: analysis, how does the compound distribute in the body of the animals, all instructing the

00:11:11: clinically development. So that's translational research for them. I like to phrase it more

00:11:17: broadly, simply to invite more people in academia to really contribute towards a research, a type

00:11:24: of research that is growing towards applications. And I give you an example how I do this in my lab

00:11:32: and what I like is so I focus our basic science and our development translational development

00:11:38: towards an application of clinical need. And to make it concrete for you in the HGV vaccine

00:11:45: development arena, it's a huge challenge to have a vaccine against this virus that is protective

00:11:54: against all the diverse variants of HGV. This is a hugely diverse virus, much greater in diversity

00:12:00: than the SARS variants that we know. So we'd like to have a vaccine that protects against

00:12:04: all of those. And then we said, well, first we have to understand this diversity and have a

00:12:08: measuring system to measure the breadth of antibody responses that are induced. Are they

00:12:13: really protective against all of them or only a few? And so that is a basic science question first

00:12:18: to say which measuring system allows us to extrapolate that would be because I cannot

00:12:23: test a million different viruses. So we used help from bioinformaticians Alice McCarty

00:12:28: and tested a range of HGVs. And then with her bioinformatics expertise and computational

00:12:34: approaches, we could define certain groups of viruses that reflect larger additional diversity

00:12:42: groups of HGV that we could then take together as a smaller subset of reference viruses we call

00:12:47: them to test the diversity of antibody responses. So that's for me a basic science question. What

00:12:53: can type of antibody responses are there against HGV? What type of virus is reflected? And then I

00:12:59: use it as an applied measuring tool to gauge human immune responses to HGV and then to benchmark

00:13:06: vaccine induced immunity. In your opinion, how great is the danger of new viruses emerging as a

00:13:13: result of, let's say, climate change and infecting us, for example, through the thawing of the perma

00:13:21: frost or zoonosis? Very honestly, I wouldn't even speak of a risk. I think it's clear that this

00:13:26: will happen at this or the other point in time. And it's the time to be prepared or to start

00:13:32: preparing. And if I look back at the past years, it is amazing what has been learned. You know,

00:13:38: if you look at the corona pandemic, of course, not every aspect has been managed perfectly,

00:13:44: but by and large, it's amazing, which I should say leaps science discovery and innovation has

00:13:51: reached and was able to develop vaccines in that short of a time. Not only this, having that had

00:13:58: just happened a few years ago, we are much alerted as to what is actually needed, what helped in the

00:14:04: backdrop of this past crisis. So we are actually very well tuned in terms of what type of research

00:14:10: we need. And it was fascinating to see the synergy of research that was collaborative across

00:14:16: countries and borders, and these helpful hands that developed these vaccines and else. But it also

00:14:22: put the spotlight on, as you just said, climate change in the ecosystems that in part are human

00:14:30: cause, not only but partly, where we have to pay attention. And that means we have to

00:14:36: focus our tools, our sentinels, our alert systems towards regions of emergence, and simply look at

00:14:44: what is there and what is the properties of what is there to do science in terms of the path, say,

00:14:50: viruses circulating there. What is the features they have? How do they make sick? Would they be

00:14:57: able to infect humans? All this could be done in the test tube in models to understand these things

00:15:05: that may emerge. And also to learn what is the type of a protective immunity that would be needed.

00:15:10: Could we devise compounds that would be broadly protective against not only this virus, but also

00:15:15: its next neighbor that I just saw circulating there. These type of things, and I hope that we

00:15:20: stay alert, not 100% as always, that's not good, but to take the lessons and to be attentive,

00:15:26: I should say, in these areas and to conduct and continue this type of work.

00:15:31: Which virus could be the next?

00:15:33: Yeah. You will hear many experts say clever things about this, and they are probably closer than I.

00:15:42: And I think it's a range of candidates. And it's interesting that the WHO has also in the top

00:15:48: pathogens that may cause a pandemic, pathogen X. And I think it's good because it hikes lights

00:15:54: that we don't know. Honestly, we don't know everything. But of course, there are certain

00:15:58: pathogens that we have a look upon specifically. These are many of the RNA virus pathogens,

00:16:04: flaviviruses of different flavors, different types of influenza viruses, for instance,

00:16:10: also different types of coronas, of course. But not only this, also the monkeypox DNA virus

00:16:16: all of a sudden was relevant. So it's important to not only think of pathogens, is it this or that,

00:16:23: but to look at ecosystems. What is in this ecosystem and what are the properties?

00:16:27: Because there may be surprises. So it's important to look at the ecosystems. And I think

00:16:31: some of the experts at Helmholtz, if I may say, at the Hy-O in Greifswald are doing exactly this

00:16:37: with the surveillance systems, the One Health surveillance systems. And they follow this vision

00:16:42: of human health is One Health. It's the whole planet that we live upon together with all the

00:16:47: beings on this planet that we have to pay attention. And that's what they do. And I think it's

00:16:53: important and not only them, many people. So it's a bit dangerous. We have to be aware. But

00:17:00: it's also very, very exciting. And thank you for the information about viruses and vaccines.

00:17:07: Yeah, yeah, very welcome. Thank you.

00:17:17: Thank you.