A virologist explains the science behind the coronavirus vaccine search
On Spec spoke with Tokameh Mahmoudi, associate professor of molecular biology at Erasmus Medical Center in the Netherlands, about the effort to come up with a vaccine for the coronavirus, and what virologists think might happen over the next few months and years.
(The interview was edited for length and clarity)
Can you tell us a little bit about what you normally do research on?
I basically run a scientific lab where we focus on research looking at HIV cure strategies. We also look at Hepatitis B virus infection, modeling it in innovative platforms. So the idea is that we’re looking for new drugs, new molecular targets in order to come up with curative treatments for these two viral infections.
How is your research about HIV useful these days when you are looking into how to develop vaccines or treatment for COVID-19?
In terms of antiviral drugs, there is a lot of talk about Remdesivir which has been looked at in the context of the Ebola virus, and there is the idea that some antivirals against HIV may also have activity against Coronavirus replication. Nothing has really been shown to definitively work yet, but there is a lot of testing looking at different antivirals that are available for different viruses — including HIV. We test them on models in which we can look for potentially new pharmacological strategies to stop COVID-19 replication.
But you must remember that COVID-19 and HIV are two very different viruses. They are transmitted differently and cause different diseases. For instance, HIV mutates very quickly — and that’s one of the reasons why it’s very difficult to develop a vaccine against it. COVID-19, as other coronaviruses, don’t seem to mutate that much… So there is some hope that developing an effective vaccine against COVID-19 will be more simple.
Listen to our coverage of the pandemic here.
Do you know much about how these antivirals generally work?
These antivirals work by blocking the polymerase of the virus. This is an enzyme that each virus has which basically reads and copies and essentially multiplies its genome so it can spread. So it’s really important in the viral replication cycle. A lot of these drugs target activity of the viral polymerase. And these are being looked at and are definitely worth testing in the context of blocking different viruses.
How do these viruses normally mutate and what happens over time?
It depends on the virus. Like I said, the mutation frequency of a virus like HIV or the flu is high. It really stems from the proofreading capacity of the polymerase of these viruses. This is the enzyme that copies the genome of the virus and amplifies it. A lot of these polymerases don’t have good proofreading capacity and result in mistakes that are incorporated into the genome of the virus as it’s being copied, essentially. What this means is that you end up with viruses or parts of the virus that are different from the original one, which may have been a version of the virus that our bodies would have developed antibodies against. If this virus mutates and changes itself, then, of course, antibodies that we would have generated against the old version, don’t do us any good anymore. So this is how viruses essentially escape the host immune system.
Some schools of thought say that as the virus propagates as time goes on in the pandemic, the virus may weaken. But another school of thought predicts this actually may result in mutations and the generation of more deadly forms of the virus… At this point in time, we don’t really know if either will occur.
Listen to our coverage of the pandemic here
But if we look from the perspective of the virus, we can see that it’s spreading very well. I would predict that in terms of its predictive mortality, it’ll probably remain more or less the same. Many scientists, including myself, also predict that it may become something like the seasonal flu. We would develop some level of immunity against this version of the virus and new mutated versions of it may emerge, probably seasonally… And we may not have quite a strong immune response against these new versions. This also points to the possible future need of seasonal vaccines, like we do in the case of the flu, against COVID-19.
Listen to our coverage of the pandemic here.
Do we have any idea how many mutations COVID-19 has undergone? Are there different strains circulating that we know of?
That’s still unclear. I don’t think there’s a lot of evidence that it has drastically mutated. There are, of course, many labs right now sequencing the genome of the different samples from patients. From my understanding, there is not a tremendous amount of accumulation of mutations that have been identified from, let’s say, the initial Chinese isolates, to warrant the idea that the virus has mutated to a weaker or stronger form. The hospitalization rates and mortality rates from COVID-19 are more or less similar and the newer mutated versions are not far different from the original virus.
Basically, there are some changes, but it’s more stable than HIV, which is constantly changing its appearance by accumulating mutations.
So HIV mutates a lot more, and it’s harder to make a vaccine that attacks the structure?
For sure! Initially, it was thought that we would be successful in developing an effective vaccine against HIV. Yet today, there is still no effective vaccine four decades after the start of the pandemic.
This is something that is not very likely to occur for COVID-19, especially given the enormous efforts and strategies to develop a vaccine.
However, this is not a guarantee, and certainly not in the short term. This points to the fact that it might be a good idea for different countries to think about strategies in which we will learn to also live in a smart and viable way with COVID-19.
What kinds of resources do labs need to do this type of work? And are those easy to come by?
In the search to develop an effective vaccine against COVID-19 — much of the difficult, technical parts — a lot of strategies are well under way. This is a massive global effort. The most time-consuming aspect of this effort is really the testing and the part that requires ensuring that the vaccine is not only safe, but also effective.
It needs to be tested in a clinical trial where part of the population receives a placebo and the other receives the actual vaccine. And then of course, time is needed to look at the numbers and determine whether it’s actually effective or not.
This is even more complicated by the fact that such trials are done with relatively young, healthy people. But COVID-19 doesn’t necessarily make young, healthy people sick. Many get infected and don’t even realize it.
Listen to our coverage of the pandemic here
Do you think the predictions that it would take 18 months or longer to come up with the vaccine are correct? I assume a lot more effort and resources are being directed out to COVID-19 than for example, HIV got over the last few decades?
Oh, absolutely. There’s no comparison. But it will take time and in order to have a definitive answer for the safety and effectiveness of a vaccine, and to produce it in large amounts where we can start immunizing the population, we will need about a year and a half or so.
Are you personally worried about the coronavirus pandemic now? What precautions do you take?
I’m not overly worried about it. We have to understand that with any pandemic, there are always, unfortunately, a lot of people who are going to die. However, what we can do right now is be realistic and think about how we’re going to deal with a world in which COVID-19 does exist, and think about the political decisions being taken and the consequences of shutting down.
Listen to our coverage of the pandemic here
This is a very complicated situation from a scientific, clinical, and capacity standpoint, and also from an economic standpoint. I think the most important thing is to build capacity to deal with patients who may need help at the intensive care level, or just general hospitalization. When that capacity is there, the only thing we can do is think about how every country will be behaving differently based on capacity and numbers. Try to see a normal life, where sick people can be treated, where the capacity to treat them at the hospital exists if they need it.
In the Netherlands for example, we have not had a strict lockdown like other countries in Europe. And we are at a stage where the numbers of admittance into the ICU have fallen, the number of dead per day, and new infections per day have stabilized and fallen, and we have the capacity to deal with upcoming peaks.
During this time, we have also allowed some level of interaction. For example during our so-called “intelligent lockdown,” children under 12 were allowed to play together. Many shops remained open, and people were allowed outside, with social distancing practices of course.
What’s also becoming clear is that in the best case scenario, a vaccine will be available in a year and a half. We have to think about building that herd immunity, slowly focusing on the healthy population to get the virus in a controlled way, develop immunity in order to then be able to protect the more vulnerable parts of the population. The idea is to try to control the infection and its transmittance. I think in the Netherlands, it’s been going very well, if you look at the numbers.
Do you have any idea why some countries don’t seem to have as big a problem as others? If you look at India, Bangladesh, Pakistan — certain developing countries that haven’t had as much of a problem, could there be some biological reason behind that?
That’s very interesting. But it could just be that these countries are still at the early stages of the pandemic. For example, in Russia, there was a large delay. Initially it seemed to be that things in Russia were under control. Now, the numbers are spiking drastically. The numbers in India and Pakistan also seem to be spiking.
Have any of your colleagues changed their research to focus on COVID-19?
Actually yes, even myself, my work involves working with South Africa on HIV. And so one of the things that we’re very worried about is what happens as this pandemic is making its way into sub-Saharan Africa, where a significant proportion of the population is already immuno-compromised with HIV infections. We have been looking at COVID HIV co-infection models.
Listen to our coverage of the pandemic here
One of the things that we are doing here at Erasmus MC is convalescent plasma transfer. Many countries have been busy with this, including China and Iran. In the Netherlands we’ve started to take plasma which contains antibodies against COVID-19 from patients who have recovered from an infection and essentially provide that to very critical patients in the ICU to try to see if they improve against the disease pathogenicity. We’re trying to get started on a similar setup with South Africa. And in this context, we can also look at HIV and COVID-19 co-infections to see if the disease is synergistic.
And I know a lot of my colleagues have shifted focus as well to using different approaches to try to understand how this virus replicates and causes pathogenicity in different models.
Have you come across any cases so far of people who have HIV and COVID-19 at the same time, and how do they fare?
Yes, and luckily, there doesn’t seem to be a synergistic effect in terms of pathogenicity with people who are co-infected. Some of this is conjecture at this point because the numbers are low, and it’s not clear. But one possibility is that since a lot of the HIV infected patients are receiving suppressive antiviral therapy, these antiviral drugs may also be effective in diminishing the level of replication of COVID-19. The situation may look very different in untreated patients who have an active HIV infection and replicating virus. But time will tell as the numbers of patients co-infected with HIV and COVID-19 inevitably increases, especially in light of the approaching cold weather in sub-saharan Africa.
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