How close is a COVID-19 vaccine? Prof. Martin Bachmann on stopping a pandemic
Written by Yella Hewings-Martin, Ph.D. on March 27, 2020
Researchers are working tirelessly towards new vaccines to stop the COVID-19 pandemic. In part one of a two-part interview with Professor Martin Bachmann, the expert immunologist spoke with Medical News Today about his vaccine, what life is like in his lab at the moment, and how he thinks the pandemic will unfold.
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While many of us are settling into our new found reality of social distancing and self-isolation to slow down the spread of the SARS-CoV-2 virus, researchers across the globe are busy working on new vaccines and treatments.
Leading immunologist Martin Bachmann is both a professor of vaccinology at the Jenner Institute at the University of Oxford in the United Kingdom and the Head of the Department of Immunology at the University of Bern in Switzerland.
Medical News Today spoke with Professor Bachmann about the COVID-19 pandemic and the work he is doing on his candidate SARS-CoV-2 vaccine. He hopes to produce enough of the vaccine to treat part of the world’s population in 6–8 months.
Virus-like particles
MNT: What are the challenges that researchers face when they work on a new vaccine during a pandemic compared to working during normal times?
Prof. Martin Bachmann: Well, it’s mostly the timeline that is so totally different. It just needs to be much faster. Normally, when we work on a virus vaccine, we have everything we need in place, the virus, the models to challenge, and how well the vaccine works.
It’s challenging now because we haven’t had the time to build up the samples, get the virus, or spend time developing the best models to use.
MNT: Your vaccine uses a different approach to what we’ve seen from other labs and companies. Can you explain how your vaccine works?
Prof. Martin Bachmann: We use so-called virus-like particles that are not infectious. These are self-assembling structures that look like a virus, but they don’t have any genetic information. If you express a coat protein of a virus, it often self-assembles into a virus-like structure.
The vaccine for human papillomavirus, for example, is a virus-like particle vaccine.
It is very well known that virus-like particles are very immunogenic. In particular, they make very good antibody responses, B cell responses to be precise. And this is what you want.
If you make a vaccine against a virus, and if you hope it works, you have to have neutralizing antibodies. Neutralizing antibodies are the key to any vaccine on the market that fights viruses.
The new coronavirus uses a Spike protein to attach to a receptor on a cell, and that allows infection with the virus. The receptor is called ACE2.
We are working with a part of the Spike protein, called the receptor-binding domain (RBD). This part of the Spike protein is responsible for binding to ACE2. For SARS and MERS, most neutralizing antibodies are directed against the RBD domain of the Spike protein.
When we use this RBD domain in isolation, it’s not very immunogenic. To improve this, we used the RBD domain, and chemically linked it to the virus-like particle.
And now, the immune system thinks that the RBD domain attached to the virus-like particle is a virus because it looks like a virus and correspondingly makes a very strong immune response. And this is the basis of many vaccines we’re developing, for example, against peanut allergy.
Testing the vaccine and making enough
Prof. Martin Bachmann: We have done a number of experiments to test the Spike protein RBD domain virus-like particle.
We used our vaccine in mice, and on the one hand, we have seen that it blocks the binding of the Spike protein to the ACE2 receptor.
We have also done what is called neutralization assays, where we measure the amount of neutralizing antibody produced after vaccination. If we vaccinate just with the RBD domain, we don’t see a lot of neutralizing antibodies. However, if we vaccinate with the RBD domain on the virus-like particle, we see a lot of neutralizing antibodies.
We then tested the neutralizing antibodies on a lab-made version of the new coronavirus, where we took the SARS-CoV-2 Spike protein and attached it to a model virus to test if the neutralizing antibodies work. Our collaborators in China carried out these experiments during the complete shutdown, and they saw that this works.
At the moment, we have a way of using chemical coupling to attach the RBD domain to the virus-like particle, and we know this works. But there is an issue with scale.
If you want to make 5 billion doses of this in a few months, you would be hard pressed to do that.
We are now working on an important modification. We are trying to genetically fuse the RBD domain into the surface of the virus-like particle. We have two different virus-like particles that we are testing for this, from the cucumber mosaic virus and a virus called AP205.
“If this works, then we expect to make around 10,000 doses with 1 liter (l) of culture, which means you can really make a lot of doses in a short period of time.”
We know the chemically coupled version of the vaccine works very well, but we would not be able to make a lot of this in a short period. We could make this for specific target groups, maybe hospital staff.
But with the genetically fused vaccine, we could make a lot in a short time. However, this needs a lot of commitment and compromises by the health authorities.
Clinical studies during a pandemic
MNT: When you are working on a new vaccine during a pandemic, which steps in the normal development process do you think you will have to skip, and what challenges does that present to you and health authorities? How are you working with them to overcome these barriers?
Prof. Martin Bachmann: We are only at the start of our conversations with health authorities now, as we’ve been working on generating the data so far. You have to focus on safety, of course. You need to be sure that you don’t harm anyone.
But, if the vaccine is pure, and it’s easy to determine whether or not it’s pure, then actually its chance to cause harm is minimal because it doesn’t replicate.
It’s not like an attenuated virus, which, if given to an immunocompromised person, has the potential to make them sick.
“So what I would like to do is an initial study, maybe on 100 people, just to see that you get the right antibodies and that people tolerate it reasonably well. Then you can expand. That would involve constant monitoring of course by the health authorities, but then really, you could give the vaccine to everyone.”
At the same time, we could work on improvements. For example, we are looking at making the vaccine even more efficient by adding adjuvants, such as microcrystalline tyrosine.
MNT: What data do you have from your previous work to show that the virus-like particles that you are using are safe to give to people?
Prof. Martin Bachmann: We have done a lot of studies. We have not tested this particular virus-like particle in humans, but we have tested it in numerous animals, including cats, dogs, and horses, and they have always tolerated it well.
MNT: How difficult will it be to do your initial studies during a time of pandemic. Who would you test your vaccine on first?
Prof. Martin Bachmann: If you want to determine efficacy, you would start with at risk people, for example, hospital staff, because you would need to have a sufficient number of people at risk of getting sick by being exposed to the virus.
But this could all be done as part of one big study. Of course, you don’t want to immunize people to then find out your vaccine doesn’t work. But testing the first group of people could already be part of a bigger study, with milestones that we would need to pass before expanding the number of people.
Well, that is my idea, at least.
Raising 100 million Swiss Francs
MNT: How do you think this might work with different health authorities around the world who do not necessarily have the same ways of approving vaccines for use in their countries or areas? Do you think now is the time to set aside these differences and just get new vaccines out to the population around the world?
Prof. Martin Bachmann: Now is probably a good time for that. With regard to the Swiss authorities, Switzerland is a very pragmatic country, and I’m hopeful that they might see the current situation with more flexibility.
Maybe we could start the program here and then expand it across the rest of the world. People are obviously willing to take some risks.
You see, the Moderna vaccine currently being tested in the U.S. hasn’t even been tested in a mouse; they have gone straight to humans. This is a very unconventional way to do things, and I don’t necessarily think that’s bad at the moment. But this would never have happened without the pandemic.
MNT: How much will it cost to develop your vaccine?
Prof. Martin Bachmann: We are in the middle of raising 100 million Swiss Francs [around 100 million US dollars] so that we can produce large amounts of vaccine ASAP.
