How Viruses Spread – Mpox, Transmission Immunology, and Global Health

00:00:00: In the middle of the SARS-CoV-2 pandemic, another potentially fatal disease breaks out in Africa in 2022.

00:00:09: Mpox. Is the world once again threatened by an epidemic?

00:00:14: Fortunately, the situation has eased again.

00:00:17: But in August 2024, the World Health Organization once again declared a public health emergency of international proportions.

00:00:27: Even if Mpox is not caused by a new virus, a variant has broken out that leads to more severe cases.

00:00:35: And one that is currently affecting many people in the Congo.

00:00:40: Epidemics are often caused by viral diseases that are triggered by new or mutated known pathogens.

00:00:47: And then the question quickly arises.

00:00:49: How is this virus transmitted and how is transmission influenced by our immune system?

00:00:55: Dr. Julia Port is dedicated to these questions and has already been able to answer them for SARS-CoV-2 and Mpox.

00:01:03: She heads the junior research group Transmission Immunology at the HZI,

00:01:08: where she combines basic research in a relatively young field of research with global health.

00:01:13: I'm sitting here in the HZI library with Julia Port. Hi, Julia.

00:01:21: Hi, Julia.

00:01:22: Julia, why was an international emergency declared again in 2024 by the WHO?

00:01:33: For the same reason that they initially also declared one in 2022.

00:01:37: So it's actually a public health emergency of international concern.

00:01:40: So it's basically already in the name.

00:01:42: It has to be of international concern.

00:01:44: So kind of a declaration that we have a disease that's causing so much damage to human lives or society or the economical situation of affected countries that we are worrying because of human life lost or just disease burden in general.

00:02:02: And it is becoming so transmissive or so transmittable across country borders that we're worrying it might become an international pandemic.

00:02:13: So in essence, it has to have that aspect of it's so much of a health burden, A and B, it's becoming so much of a transmission burden that we think it is of international relevance because the damage to the whole of humanity could be significant.

00:02:29: Is the Mpox virus of 2024 the same as the one of 2022?

00:02:38: Not exactly.

00:02:39: So basically Mpox itself has existed for decades, or we've known about it for decades.

00:02:45: And traditionally, there have been two different clades, clade one and clade two that were sort of assigned to different geographical regions in Africa because that is where they were mostly found to be endemic.

00:02:56: And the 2022 outbreak, similar to I think the 2018 outbreak in Nigeria was caused by clade two.

00:03:05: And then the 2022 one became a sub clade of two B. And that is what was responsible for that outbreak.

00:03:13: And it's still circulating actually is not completely gone.

00:03:17: But the current outbreak of the Democratic Republic in Congo is actually caused by clade one, majorly by a new clade one B that appeared now for the first time.

00:03:27: And it's also related to a lot of human to human transmission, but there's also circulating continuous spillover events and outbreaks from clade two A, which is the traditional clade one A, the traditional clade one.

00:03:41: So I think it's very, very complex. And yeah, there are two clades with two sub clades each.

00:03:50: But in general, what kind of virus is it? Is it linked to the smallpox virus?

00:03:56: Yeah, it's also a pox virus.

00:03:58: Basically, pox viruses as a family have evolved with different species for a long, long period of time and have sort of adapted to their specific host of choice.

00:04:11: So smallpox was the one that was kind of circulating in humans.

00:04:16: Mpox is kind of misnamed, which is also why it was previously known as monkeypox, because it was first found in a monkey, but that is actually not the reservoir species of this pox virus.

00:04:29: We don't know what the reservoir exactly is, probably a small rodent or a small monkey in that that is found in Central or East Africa.

00:04:38: And it is basically adapted to that reservoir species and now causing spillover events and human to human transmission as well.

00:04:46: But in as much as that it's similar to smallpox, the vaccine is actually cross protective, which is also one of the suspected reasons why we're seeing an upsurge in monkeypox cases now, because the smallpox vaccination has been stopped and basically the population that was protected is dying off.

00:05:04: Okay. How is the Mpox virus the transmission way? How is it transmitted and who is particularly at risk?

00:05:13: So maybe we separate an endemic transmission and epidemic transmission.

00:05:18: So classically, when we looked at endemic transmission, which is what we saw for the last 50 years, it's normally started by a small spillover event from the suspected reservoir to most likely a child.

00:05:30: And then we had some within family human to human transmission or healthcare setting transmission, but it was very localized and small clusters.

00:05:40: And then now we have these newer subclades. So to be and one be that have more human to human transmission.

00:05:51: Though we're not super certain yet if this is virus intrinsic capabilities, or if by chance they have managed to access transmission routes that just previously weren't as prevalent.

00:06:05: So therefore the transmission itself actually happens because you have contact with the virus.

00:06:10: Traditionally, if you're interacting with this reservoir species, maybe because you have a broken wound, you have a bite, you're handling animal pieces for whichever reason you're going foraging or hunting in the forest.

00:06:23: And with human to human transmission, the risks are because you're having contact with your skin, no more coastal surfaces with contagious liquids and fluids from an infected person.

00:06:34: You have basically close to very close skin to skin contact, you may have potentially transmission through droplets when an infected person is exhaling them.

00:06:44: Though that is not the major confirmed route. It's truly just close personal contact, which is also why the sexual route is very easy for this virus.

00:06:55: Okay. And how can you protect yourself from impacts? And how dangerous is the virus actually for us? You mentioned the vaccination.

00:07:06: Yeah, maybe I'll start with how dangerous this virus actually is. I mean, if we look at the case fatality rates, there's actually been past outbreaks where the case fatality rates were higher to a degree where you would say this is truly life threatening for a lot of people if this would become a global outbreak.

00:07:24: Of course, in addition to lethality, there is mobility and it's truly a disease I would not wish to have, but would wish on anyone to have because the source and the post chills and it can be extremely painful.

00:07:37: So it's very just is not like having a mild case of SARS-2, for example.

00:07:43: So is it super dangerous in regards to high mortality? The answer would be no. Is it dangerous from how well it transmits currently? The answer would also be no, because you still require this close human to human contact.

00:07:58: And in essence, stopping close human to human contact should be quite easy because the only thing you need to do is tell people to stop having that close contact or use protective measures to reduce the risk of being exposed to a fluid that is containing the virus.

00:08:12: When having close contact with another person. So that would also be the suggestion of how you can protect yourself.

00:08:18: Basically, if you are in close proximity to a person that has this virus, you can use any kind of measurements such as wearing a mask, wearing gloves or anything, any kind of protective equipment that you have access to to sort of shield yourself and your environment from potentially encountering this virus.

00:08:38: That's that sort of the things that you can do. And on top of that, there is a vaccine, which is not wildly suggested for everyone right now in Germany, just because the assumption is that we're currently not facing a pandemic that would easily spread within Germany.

00:08:54: Also, because of the fact that Germany has a very different healthcare setting than, for example, the DRC currently has and also very different social structures than what the DRC currently has.

00:09:06: Here it's advised to be given to risk groups. Risk groups, classically, are people with weakened immune systems. Also, for example, children or people that have HIV.

00:09:17: Any kind of immune suppression would be a very bad combination with this virus.

00:09:23: And then you have a potential risk group also with people that might have to have close contact with infected people where they cannot protect themselves.

00:09:32: So your research basically focuses on the spread of viruses and you received the Helmholtz Investigator grants and have been leading the transmission immunology junior research group at the age that I since May 2024.

00:09:48: What are the main goals of this research group?

00:09:52: So very, very broadly put, the goal is to provide some fundamental science research to increase our pandemic preparedness in case we are facing another pandemic that might become prevalent in Germany with the, let's say, path to analyze how our immune system,

00:10:12: either our innate or our adaptive immune system is actually on mucosal surfaces fighting virus infections in such a way that it's actually stopping the secretions of virus or the exhalation of virus into the environment.

00:10:29: So we're studying basically the interplay of the host with the virus and the environment to understand holistically, but also mechanistically why or why not we are exhaling virus or shedding virus in other respiratory fluids or other body secretions,

00:10:46: depending on which virus we're looking at and what we can actually do with therapeutics with vaccines or with non-phymaceutical mitigation strategies to decrease the burden of virus in the environment.

00:11:00: Okay.

00:11:01: You mentioned the mucosa and you have developed models to study the transmission of the Mpox virus via mucous membranes.

00:11:09: What were the most important findings from this research?

00:11:13: Yeah, I think there were, let's say, two sides to that question and the answer to that question.

00:11:18: And I'll start with the scientific findings that this research provided.

00:11:22: So we set up a new small rodent animal model to look at different exposure routes to sort of investigate very fundamentally whether, let's say, mucosal uptake of this virus leads to increase disease and increased onwards transmissibility compared to, let's say, uptake through the skin.

00:11:38: And we found that rectal and vaginal inoculation of the rod model that we developed actually really facilitated increased amounts of viral replication within that host, but then also increased shedding and also led to more transmission to naive animals as compared to skin inoculation,

00:11:55: but also interestingly as compared to aerosol uptake of the virus, which sort of suggested to us that the outbreak in 2022 caused by Clay-2B, which is the one that we used for these studies, was potentially not just driven by human-to-human behavior, but also because of the intrinsic ability of this virus to really love mucosal surfaces and get into a host and out of a host through those surfaces.

00:12:19: And on top of that, we also found that immune signatures by T cells and B cells actually were variable depending on which exposure route was used, really suggesting that immune pathogenesis for this virus is different depending on the exposure route and therefore suggesting that potentially vaccines or therapeutics could also be targeted specifically to the most prevalent exposure route that we're currently having a problem with.

00:12:42: The second level was that it's actually very worthwhile to look into old literature and even literature from the 70s or 80s sometimes, because sometimes you can find niche knowledge and that's one of the examples where we built an animal model based on a single sentence in an obscure publication.

00:13:01: publication.

00:13:02: with the hope that it would work.

00:13:04: And we realized that it worked beautifully

00:13:06: if we're adapting it to the human situation

00:13:08: and using exposure routes that are very relevant

00:13:10: to what's currently happening on a public health perspective,

00:13:14: as opposed to using, let's say,

00:13:15: more traditional inoculation routes

00:13:18: that would have been the textbook route

00:13:20: to start with if you're wanting

00:13:22: to develop a new animal model.

00:13:24: - Okay, so you went your own way

00:13:27: and your work combines immunology, virus ecology

00:13:31: and virology.

00:13:33: What are the challenges and benefits

00:13:35: in this, let's say, interdisciplinary approach?

00:13:40: - I think the clear benefit is that you can ask

00:13:42: holistic and mechanistic questions about a whole process.

00:13:44: In this case, for example,

00:13:46: exhalation of an airborne virus from a host

00:13:50: based on the immune signature of that host,

00:13:53: looking also at how that virus survives in the environment

00:13:56: and how it enters a new host.

00:13:58: And we can look at all of them together.

00:14:01: And that is, of course, really critical

00:14:02: for the design of mitigation strategies

00:14:04: that want to prevent the transmission of that virus.

00:14:08: The disadvantage is that it's, of course,

00:14:09: so new that there's no course or degree

00:14:14: that people can take to study transmission immunology.

00:14:16: And therefore, any student that comes to my lab

00:14:19: has to learn a whole host of new information

00:14:21: that they will have not encountered

00:14:22: in their previous experience.

00:14:25: And therefore, also the communication

00:14:27: from the group of people that work on, let's say,

00:14:29: more the ecology side or more the innate immunology side

00:14:33: is sometimes not the easiest

00:14:37: because sort of everyone has to be aware

00:14:39: of all these different topics.

00:14:41: And the other disadvantage is that

00:14:43: because we're brought in this, we cannot be super specific.

00:14:47: So someone who's truly just studying

00:14:48: the aero biology of MPox

00:14:51: would get much more detailed understanding

00:14:54: and perhaps use more refined techniques

00:14:56: to go into the nitty gritty of this

00:14:58: than what my lab would do.

00:15:00: - Okay, so you have also to do a lot of management

00:15:04: and communication.

00:15:05: What can we learn from the MPox

00:15:08: or your MPox research for other viruses and for the future?

00:15:13: - I think we can learn two major lessons.

00:15:15: One is that it's super relevant

00:15:18: that you have to have a structure internationally

00:15:21: in place where research is robust, reliable,

00:15:24: and also with a long-term vision.

00:15:28: So it really is unfortunate if hot topics are dropped.

00:15:31: We would probably have been faster with SARS-2

00:15:34: if more labs had continued working on SARS-1,

00:15:36: but of course the virus was gone,

00:15:38: public interest had decreased,

00:15:39: the funding decreased as a result of that.

00:15:43: And therefore, so knowledge and skills are basically lost.

00:15:46: So we were able to build up an MPox model really quickly

00:15:50: because we had a lab that was already set up

00:15:52: to work withpox viruses, had a past interest

00:15:55: because we were able to work with collaborators in DRC

00:16:00: and therefore we could build upon pre-existing experience.

00:16:05: And that is incredibly useful.

00:16:09: And it doesn't necessarily have to be

00:16:10: your own pre-existing experience,

00:16:11: it can be that of a field,

00:16:13: even if the field had been neglected, so to say.

00:16:16: And the second thing we can learn from it

00:16:18: that you have to address the urgent questions

00:16:21: in as much as that you need to be willing

00:16:23: when you're addressing them

00:16:24: to also rethink dogma or rethink your experimental approaches,

00:16:29: because we would have never been able

00:16:30: to set up this annual model

00:16:32: had we stopped at the textbook inoculation route

00:16:34: because it simply did not work.

00:16:36: - During the SARS-CoV-2 pandemic,

00:16:39: you also worked on urgent public health issues.

00:16:42: How do you see the link between basic research

00:16:46: and rapid reactions to health crisis like this?

00:16:51: Yeah.

00:16:52: So you basically cannot have a rapid reaction

00:16:55: to a health crisis

00:16:55: if you don't have use of fundamental research

00:17:00: leading up to it.

00:17:01: 'Cause you need, like I said, this robust structure

00:17:03: of people that actually know how to work with certain viruses

00:17:06: or bacteria or whatever pathogen of choice

00:17:08: and have the infrastructure to then tackle the questions.

00:17:12: And they're never gonna have the infrastructure

00:17:14: if they don't do fundamental science first.

00:17:17: And I think even amidst the pandemic,

00:17:19: you have a place for fundamental science

00:17:21: because it won't be the last pandemic.

00:17:24: So even if the question is not the most urgent

00:17:26: from a public health perspective,

00:17:27: it's probably still very relevant

00:17:29: or can be relevant in a couple of years.

00:17:32: But my research itself, I mean, it is fundamental

00:17:36: in as much as that I'm trying to understand

00:17:38: mechanistic aspects of transmission,

00:17:41: but the questions are driven by what we currently do not know

00:17:46: and what we need to know to make human life better.

00:17:49: So therefore it's, let's say, fundamental science

00:17:52: inspired by public health requirements.

00:17:54: - How can we as a society better be prepared

00:17:58: for future pandemics?

00:18:00: You said they will come, yeah.

00:18:02: And what role does science communication play in this?

00:18:05: - So I think we as a scientific community

00:18:10: can be better prepared in as much as

00:18:14: that we keep this institutional knowledge

00:18:15: but also generational knowledge.

00:18:18: And that let's say young people are not starting from scratch

00:18:21: or trying to think that they need to rewrite

00:18:24: what older generations have basically put in place.

00:18:27: And I think that there is also what I said before,

00:18:31: neglected diseases are only neglected for a certain time

00:18:34: and the work people do on them is incredibly valuable

00:18:37: once they're not neglected anymore.

00:18:39: And I think there we can learn that investing

00:18:43: into what we think is not important

00:18:46: might be a good strategy.

00:18:48: From a societal level, I think we had a lot of trust lost

00:18:54: and miscommunication unfortunately occurred

00:18:57: during the pandemic because most people never really learn

00:19:02: for various reasons how science actually works

00:19:05: and what is done to produce a publication,

00:19:09: what is done to produce a white paper and so on and so forth.

00:19:13: And I think they're some more fundamental understanding

00:19:15: of how these processes work and being able to teach people

00:19:19: to be able and strong in reviewing scientific findings

00:19:24: even if they're not scientists themselves

00:19:26: will be quite helpful to shorten the communication path lines

00:19:30: but also patience because I think one of the key problems

00:19:34: we had is that we moved so quickly

00:19:36: that the knowledge translation from the scientific lab

00:19:40: to the kitchen table at home was perhaps too fast

00:19:44: in a way that critical steps in the middle

00:19:46: or proof reading sort of was skipped.

00:19:50: So I think a lot of scientists can improve

00:19:55: their own scientific communication skills, myself included

00:19:58: because it's not traditionally something we learn

00:20:00: on how to rewrite our science into something that,

00:20:04: let's say my parents would understand.

00:20:06: And I think that's a very valuable skill

00:20:09: that we need to improve on.

00:20:11: And then as a whole, what can we do to prepare?

00:20:15: I mean, a willingness to potentially put the well-being

00:20:19: of a population above the well-being of an individual

00:20:23: but that's a really hard sell if you're asking people

00:20:27: to engage with mitigation strategies

00:20:29: that feel over the top or untargeted.

00:20:32: - So it's a very big challenge that lies before all of us,

00:20:40: I think, no?

00:20:41: - I think so.

00:20:42: - Yeah.

00:20:43: How did you actually come to this research topic?

00:20:47: - I think fundamentally because my parents left some books

00:20:50: in the library when I was still reasonably young,

00:20:54: such as "Hot Zone", which I found as a child

00:20:57: to be very engaging and very interesting.

00:20:59: I thought, well, it would be very fun to be someone

00:21:01: to research emerging diseases that people don't understand.

00:21:06: Funny enough, not 20 years later,

00:21:07: I know some of the people that feature as characters

00:21:10: in these books and of course the reality

00:21:12: of what actually happened is very vastly different

00:21:14: from what the book version would tell you has occurred.

00:21:18: But I think it set me on this path

00:21:21: and I did quite a bit of my time focused on tropical medicine

00:21:25: which is still where my passion lies

00:21:27: in as much as that I found zoonosis to be super interesting

00:21:31: in the aspect that we have a disease that occurs

00:21:34: in a reservoir, a disease that occurs in humans

00:21:37: and it's not the same.

00:21:39: There is something dramatically different

00:21:40: than the immune response in human versus the reservoir

00:21:43: which is super engaging in the context

00:21:46: of why that is the case,

00:21:47: like why it does one die and the other survive.

00:21:50: And I think we can learn a lot of fundamental aspects

00:21:53: about immunology and good immune responses

00:21:55: from that conundrum.

00:21:57: And also because we have different exposure routes

00:21:59: and these exposure routes create different disease phenotypes

00:22:02: and immunopasogenesis.

00:22:04: And that's a super interesting question as well

00:22:06: of why our body is better at controlling something

00:22:08: if it comes in one way than if it comes in through another.

00:22:11: Yeah, so I stumbled through a couple of chapters

00:22:15: in virology, immunology

00:22:16: and then a bit of more ecology oriented virology.

00:22:21: And that sort of brought me to the point was like,

00:22:23: well, it would be really cool to combine them

00:22:25: because then we can actually study transmission

00:22:28: within the framework of also studying the host.

00:22:31: And that's where we are now.

00:22:32: - Is there any advice you would give to young researchers

00:22:37: who went to join this field?

00:22:40: - I think the advice would be that you can join this field

00:22:42: from various angles.

00:22:44: And you need to pick the one that suits you the most

00:22:47: because there's no way you're gonna be an aerobiologist

00:22:50: and immunologist and a virologist.

00:22:52: And I'm still on the side where I would say

00:22:55: I'm an immunologist by training

00:22:57: and I dabble in the other two fields.

00:22:58: And I think you need to make that choice for yourself.

00:23:01: What is your primary interest?

00:23:04: And then find a question that you find really interesting.

00:23:06: And then that the question drive your passion for that field

00:23:10: because in my case, I hated immunology as a student.

00:23:13: And then realize that the questions I want to ask

00:23:16: actually made immunology fun and really interesting.

00:23:19: And then there you have it.

00:23:20: I think if you find the questions that give you passion

00:23:22: then you can get the rest of it lined up.

00:23:25: - So I think you work very, very much.

00:23:31: But do you have free time?

00:23:34: Some kind of free time?

00:23:35: And what do you do in your free time?

00:23:37: - Yeah, I take the free time

00:23:38: because I think during the pandemic,

00:23:40: a lot of people realize that if you don't,

00:23:42: you're gonna skit towards a burnout

00:23:45: or gonna have an unhealthy lifestyle

00:23:47: because I learned from my past mentors that you work

00:23:51: because you might enjoy work or you should enjoy work.

00:23:54: If you don't enjoy it,

00:23:56: then there's no reason to be in science

00:23:58: but in my own personal opinion.

00:24:00: But you also work to have a life.

00:24:03: And I think that life is equally important.

00:24:05: So yeah, I do have free time

00:24:07: and I normally spend it outdoors.

00:24:10: I have various outdoor hobbies.

00:24:12: Key featuring would be snowboarding, scuba diving,

00:24:17: hiking, kayaking.

00:24:18: I spent the last four years living in Montana.

00:24:20: So it was quite easy to have outdoor hobbies

00:24:22: not at a mountain and brown track.

00:24:23: I'm reevaluating and have to figure out what we can do here.

00:24:27: But you need that because otherwise

00:24:30: you're never gonna be as productive in your work

00:24:32: if you are not living a good life in your private life.

00:24:36: - Last question, do you perhaps have a few tips for you

00:24:41: for our listeners as a take home message

00:24:45: on how we can best protect ourselves from infection

00:24:49: with maybe zoonotic viruses?

00:24:51: - Maybe two tips.

00:24:52: One, for the sake of zoonotic viruses,

00:24:55: I guess the easy answer would be

00:24:57: don't go travel where the reservoirs live.

00:24:58: And if you go travel where the reservoirs live,

00:25:01: know how to protect yourself from engaging

00:25:03: with said reservoir animals.

00:25:05: If we're already facing human to human transmission,

00:25:07: then my tip too would be don't put the focus

00:25:10: on the person trying to not get sick,

00:25:12: but put it on the person who's already sick

00:25:13: and enable them to feel like they have the right

00:25:17: to wear a mask, disinfect their hands,

00:25:19: not go to work because they're sick.

00:25:22: If we as a society would recognize

00:25:24: that it's perfectly okay to be sick

00:25:27: and be away from other people because we are sick

00:25:31: and have other people pick up your societal responsibilities

00:25:34: while you're sick, then I think a lot

00:25:37: of the other measurements would fall in place really easy.

00:25:40: - I think this is a very, very good advice.

00:25:42: Thank you for the interesting information and for your time.

00:25:47: - Thank you.

00:25:47: - Julia Park researches how viruses spread,

00:25:50: especially zoonotic viruses,

00:25:52: and how our immune system reacts with that.

00:25:54: (gentle music)

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