On a chilly December day, with the trees along the Cherwell standing bare against the winter sky, I took a stroll around Addison’s Walk with Professor Maheshi Ramasamy. Maheshi has been a Magdalen Fellow since 2020, and as Florey Lecturer she’s the Lead Tutor for all Graduate medical students at Magdalen. Her research focuses on developing novel vaccines for emerging pathogens.
Maheshi was a principal investigator on the Oxford-AstraZeneca vaccine during the pandemic and is currently working on a new vaccine trial for the Lassa virus. Accompanied by her dog, Plato – who was much more interested in the squirrels than in vaccinology – we discussed the long road from the lab to the clinic.
This month, it’s the five-year anniversary of the first ever Oxford-AstraZeneca Covid Jab. Brian Pinker, who was 82, was the first person to receive the life-saving vaccine outside of clinical trials at Oxford University Hospital.
This conversation was originally part of the Addison’s Talks podcast, where we take a walk with one of our academics on the circular walk around the Water Meadow to discuss their work and research. This is episode four of the series, and you can listen to other interviews here.
You’re working on a new Lassa vaccine trial; do you want to tell us a little bit about that?
Lassa fever is a viral haemorrhagic fever, so it’s a really serious illness caused by a virus very similar to Ebola, which many people will have heard of. It largely affects people in West Africa, and has a high mortality rate. Severe cases can cause fever, bleeding, multi-organ failure, and death.
It’s spread by contact with contaminated faeces of a kind of rat called the African natal rat, and it’s a particular problem in pregnancy and for healthcare workers who are looking after people with Lassa fever. There’s no treatment for this disease and no vaccine as yet, and so what my group and I are trying to do is develop a new vaccine to protect people.
What is happening in the trial now?
My trial involves taking this new vaccine – which takes a part of the Lassa fever virus and incorporates it into the same platform we used for the Oxford-AstraZeneca Covid-19 vaccine – and running a first in-human trial here in Oxford. The idea is that we will then roll out to West Africa; we’ve got trials in Nigeria, Côte d’Ivoire, and Liberia.
Does this function the same way as the creation of the AstraZeneca vaccine?
With all drugs, you’ve got a very staged way of making sure the drug is safe and effective. You’ve got lots of checkpoints with regulators and ethics committees. It’s exactly the same with vaccines and that’s exactly what we did during Covid-19.
People often ask how we managed to get a licensed vaccine within a year. The difference then was that we had a lot more resources – financial and people – and we were communicating with regulators on a rolling basis. Normally, you do phase one, wait for data, then apply for funding, then do the next trial. That can take 10 years! In Covid-19, as soon as we had final data from phase one, we could move into later phases. That’s what allowed us to get “needle in arm” quite so quickly.
How does it work? Do you give them the vaccine and then try and expose them to the virus?
Not in this case, because Lassa is a pretty dangerous virus and it wouldn’t be ethically right. What you’re describing is what we call a Controlled Human Infection Model.
We’ve done that very successfully in Oxford with things like malaria and typhoid fever, where volunteers drink a solution of bacteria or are exposed to a specific dose of a bug. It works, but it’s got to be for the right bug, and you’ve got to do it very carefully.
Lots of people get vaccines, but there are quite a few people who might feel more hesitant about getting them. Why do you think that’s happening?
It’s an interesting question. We used to think about vaccines really just for babies, as their immune systems are more immature, they’re more at risk of diseases like pneumonia or meningitis so we vaccinate against this. But over the last few decades, we’ve seen the importance of life course vaccinations, such as protection for pregnant women, older adults, or people who are immune-compromised; like the yearly flu Jab, or the shingles vaccine for the elderly.
Vaccines save so many lives; the WHO estimates that in the last 50 years alone, vaccines have saved over 150 million lives. But because of that success, people don’t see these diseases anymore. We don’t see children dying of tetanus or polio in this country. Since the pandemic, I think there is a real positive in that people understand the rationale better; people know a lot more about vaccines than they used to – which is great!
In some vulnerable communities, though, there is some mistrust; and maybe that’s got worse since Covid. Some people might feel like vaccines weren’t designed for people like them – which is why it’s important to make sure you’re testing across a wide range of people – and I think things like vaccine mandates weren’t handled particularly well. People need to make an informed decision, the one they think is best for them, based on the evidence.
What do you think the future of immunisation is going to look like?
We are at an exciting point. We are developing lots of new platforms and have the ability to design vaccines against many different bugs, including antibiotic-resistant bacteria. We’re preparing for future pandemics by designing a library of vaccines against viral families that could cause outbreaks.
But there’s still a challenge in getting them into arms. in the UK, we’re really lucky that we have a really good public health system. The Department of Health provides vaccines for free for everyone who needs them. However, there are around 50 million zero-dose children in the world who haven’t had essential childhood vaccines. Organisations like Gavi, Médecins sans Frontières, the Vaccine Alliance, and UNICEF all do fantastic work delivering vaccines into places that are hard to reach for many reasons, and it’s vital that they continue to be supported.
What does it mean for the wider community when immunisation is successfully implemented and as many people as possible are vaccinated?
Vaccines are one of the most brilliant tools we have in medicine, and they don’t just protect the people who are immunised. If you get, for example, a measles vaccine, you’re protected from measles, but you’re also protecting other people in your community from measles. This is the idea of herd immunity.
It’s not just about protecting people in the here and now, either. That works well for some vaccines and some diseases. With flu, you have a seasonal vaccine every winter that protects you for that season, but the HPV (human papillomavirus) vaccine stops you from getting cervical cancer and potentially head and neck cancer in the future, which is caused by these viruses.
So, there is a real health benefit either now or in the future. For me, vaccines are a no-brainer; the benefits are everywhere.
Finally, if you could take anyone on a walk around Addison’s, who would it be and why?
As a female vaccinologist, I’m going to have to opt for Lady Mary Wortley Montagu. She was actually the wife of a diplomat in the 1700s. People often think about vaccination and Edward Jenner and the whole story of cowpox and taking the milkmaid scabs and inoculating his son. But actually, this was based on a process called variolation, which was practised in the Middle East and in China for centuries and centuries.
People realised that if you took the scabs from somebody who survived smallpox – which at that time was an almost lethal disease – and you put that in a cut in somebody who was healthy, they were protected from smallpox. This is the very first vaccination. Like I said, this had been practised for centuries before Edward Jenner.
Lady Mary Montagu observed this practise when she was travelling in Turkey with her diplomat husband; she variolated her own children and brought the practise back to Europe, really influencing people into seeing variolation as a useful practice and advocating for early vaccines. I reckon she was probably a pretty cool woman. She was ahead of her time. A female vaccinologist. So yeah, I’d bring her on a walk with me.
Thank you so much to Maheshi – and, of course, Plato – for joining us on a walk in the mid-December chill. It was fascinating to spend some time talking all things vaccines and variolation, with a few inevitable interruptions from the local squirrels along the way.
If you’re interested in hearing more from our brilliant academics here at Magdalen, you can listen to more episodes of Addison’s Talks, or follow us on our social media for the latest updates.