No sooner did Western media reports emerge of an outbreak of mpox in Africa than there appeared reports of cases detected outside Africa. People began to think more about the spread of this virus. Especially in the wake of the Covid-19 pandemic, which left millions dead around the world and disrupted economies and societies in ways still being felt, many people have wondered about the ability of mpox to become another global pandemic, and what can be done.
To learn more, The Voice talked with Dr. Melanie Ott, director of the Gladstone Institute of Virology, part of the Gladstone Institutes in San Francisco. Dr. Ott, who is also a professor of medicine at UCSF, leads a team of virology researchers at Gladstone investigating the “viruses of today to be prepared for the viruses of tomorrow.” She and her team are looking closely at mpox to find ways to apply their technologies so they can make a contribution to the global effort.
Let’s cover the basics of mpox. What is it? I understand that there are two clades [variations of the virus with a common ancestor], and one of these clades is more dangerous than the other. Give us a bit of a background on mpox and then specifically about this outbreak.
Mpox has been, I would say, the small cousin of smallpox. Smallpox was eradicated through a very courageous and systematic vaccination campaign that has also kept mpox and other pox viruses at check. Why we are hearing now more about mpox is because this immunity that was used and induced to eradicate smallpox is now going away. There were predictions in the past that other pox viruses might make a comeback or a first appearance.
Mpox is a virus that we have heard of more in the last few years and [it] is now unfortunately spreading in two clades. As you correctly pointed out, there is classically a West African clade that we know quite well. There was a 2022 outbreak that was scary, which got everyone alerted to mpox. This clade is much less dangerous and problematic. Now we have a new outbreak in Congo that is a mixture of clade I a and b, and which is classically known to be a much more severe disease induced by this clade.
[People] in San Francisco reading about what’s happening in Africa — and then we’re starting to see stories that Thailand has confirmed a case, I think Sweden had confirmed a case —
Sweden. Yes.
What should people be thinking about and what should they be aware of?
There are defined risk groups, and if you belong to that risk group, you should maybe think about getting vaccinated. We are much luckier with this virus because we have a functioning vaccine that is effective against this clade. So I think the vaccine is a very important tool. It’s not going to be rolled out for everybody, because this mpox is less problematic than SARS Covid. In terms of transmission, it’s much, much harder to get mpox. It is mainly transmitted, currently, through bodily fluids, very close contact — sex and contact with infected lesions. There is a respiratory route, but that involves very close facial contact. It’s less than you going in the airport and you can contract mpox; much, much, much less likely than, for example, contracting the new variant for SARS-CoV-2. 🡪It’s far less likely of contracting mpox, for example, in an airport than it would be of contracting the new variant for SARS-CoV-2.
You said earlier that the immunity from smallpox is starting to go away. Is that just because we got rid of smallpox so people are not continuing to be inoculated?
That vaccine campaign was stopped, and I think that leads to more people not being more immunized any more.
People who were immunized when they were younger — are they still immunized or does that wear off?
Yes, usually that immunity is long, and it definitively will confer some protection.
What sort of things are you looking at or where do you see you and your team contributing?
The interesting part about mpox is it’s a DNA virus and not an RNA virus like the coronavirus. We have always talked about the coronavirus being a big virus and having a big genome. Mpox is much bigger. We are working on RNA viruses, so it’s a leap to go into a DNA virus. But we have established several tools in the lab that we can employ. We are doing diagnostics, specifically with CRISPR. And I think we can do this. This is something that can be easily reprogrammed for many viruses. I see a need here for wider screening and testing, because again, there’re people who have severe impacts, but there’s also people who have undetectable or not clinically obvious mpox. So we don’t know really what is the infection rate and what is circulating. I think that’s going to come.
‘Have we learned, are we sustaining what we learned? I think we have been yo-yoing a little bit.’
So I think diagnostics is something we can contribute. We have in the past year developed some technologies to engineer viruses — we can build natural viruses in the lab. We’re not inventing new and dangerous viruses, but if there is a virus circulating in Congo, for example, instead of waiting until we can get access to it, we could make that virus now in the lab. The Congo virus is a very high-security virus [and there] is currently no plan for us to replicate [it] in the lab, but there are several tools we can use to study the virus. One is the vaccine strain that has been used. It’s a widely used virus, and it’s an attenuated virus — a virus that is not dangerous and replicates much less in humans and induces immunity — and we can use that without any problems in the laboratory.
We can also work with a clade II virus under the appropriate biosafety measures that we have at Gladstone. So we have both the viruses and the permit to work with it so we can start learning about the virus, getting it into cell culture, understanding how it behaves, [the] requirements it has in the cell to be successful, and where its Achilles heels are. We are interested in therapeutics; finding better treatments. There’s no dedicated, approved drug for mpox. There are drugs for smallpox that have been repurposed for mpox and which have some efficacy there, but I think there’s no direct mpox treatment currently available.
So I think these are all areas where we see possibilities for us. We have great immunologists in the institute in different labs: Nadia Roan, a great immune virologist, and we have just hired a young new star in the vaccine technology world, Magnus Hoffmann from Caltech. So there are various approaches we can take to look at viruses and new viruses.
When the Covid 19 pandemic hit, obviously the populace in general was unprepared, but there were a lot of governments unprepared and a lot of processes that were not in place — stockpiles that had not been kept up, and so on. Are we as a result of having gone through that better prepared now for the next pandemic?
This is an important question, and probably a reminder that we might not follow all of the good intentions that we had a few years ago, and [are] not putting the money where we should potentially have put the money. It’s a very difficult question. I think stockpiling vaccines — they expire and you have to redo them. But what I see as really critical is to boost the basic science in the virology field so we don’t have to go from zero to a 100 when the virus is showing up, but we can actually go from 40 to a 100 and then that will give us a huge leg [up] in responding.
Let me explain. When you look at the SARS-CoV-2 vaccines, everybody said, O.K., these are coming out of nowhere. All of a sudden we do RNA [Ribonucleic acid], all of a sudden we get a successful vaccine strategy with a spike protein.
What we don’t see, and what I don’t think that the public fully understood, is that this was not coming from zero, but this was coming from 40 instead of zero, because there was a lot of research going into the mRNA vaccines in other contexts. And there was a lot of research done on the immunogen based on SARS Covid I … and this was very quickly translated into SARS-CoV-2, and that’s why this could be so effective.
A lot of people rightfully were skeptical and said we can’t produce something from zero to a 100 in a year. They’re totally right. But we can produce something in a shorter time where we already know a lot. We need to be strengthening the basic research and the knowledge about these things and different classes of viruses so we are prepared when a new virus comes to actually tap into that research and use it for a successful translational strategy, vaccines, therapeutics, and so on.
Are there other potential viruses out there that you’re keeping an eye on and that maybe the general public might want to know about too?
Well, we have good tools. We now have wastewater sequencing, which is good; we know that we are now a [single, connected] world, so things are coming from outside and might come into our wastewater when it’s too late basically. So that’s one of the good developments that I really like. But I think the connection with other wastewater surveillances in other countries might be very important.
I keep my eyes very closely glued to H5N1, which is the bird flu, because that has now jumped into cows and into sea mammals and into others. Influenza in general is something that we all know every year through the flu vaccine. And I very much encourage everybody to continue to get that vaccine because it [also] provides a protection against upcoming new viruses.
There’s a little bit of a fatigue. Coming back to the comment that you made: Have we learned, are we sustaining what we learned? I think we have been yo-yoing a little bit. We have been very interested, and now everybody has a fatigue and nobody wants to talk about coronaviruses, and interestingly also influenza viruses. I think we should not do this. We should still invest in both coronaviruses and influenza viruses, because they’re the ones that have the longest history in coming back, mutating, and causing harm to humans in periodic timeframes. This is not going to change in the future.
Our world is changing. We are living closer with animals. We are closer connected with everybody globally. If a virus is somewhere in the world, it will eventually come here. And that’s the same for this mpox virus. It’s not going to stop at the border. It’s only a matter of time, and this is always the case.
Edited for length and clarity.
