Part 6 of our Malaria Gamechangers series (check out Episodes 1-5) highlights the R21/Matrix-M™ [R21] malaria vaccine, a high-efficacy malaria vaccine targeting young children who are most vulnerable to the disease.
Developed by the University of Oxford’s Jenner Institute, R21 is currently in the late stages of clinical trials and has demonstrated promising results thus far. A recent Phase II trial in Burkina Faso showed that R21 was up to 80% effective in preventing severe malaria among young children who took all three doses and the booster, with protection lasting at least 12 months. This trial enrolled 450 children in an area of highly seasonal malaria transmission. Now R21 faces a greater test: an ongoing Phase III trial has enrolled 4,800 children in numerous East and West African countries of both seasonal and year-round transmission.
Phase III trial data will be released later this year; and if the vaccine continues to demonstrate high levels of efficacy and safety, it will likely become the second-ever malaria vaccine approved by the World Health Organization for widespread use. In the meantime, Ghana and Nigeria have already approved the use of R21 – a significant development considering that one-third of all malaria deaths among children occur in these two countries.
To accelerate distribution, the University of Oxford has partnered with the Serum Institute of India, which has the capacity to produce up to 200 million doses annually. This partnership ensures the vaccine won’t face the same manufacturing hurdles that other vaccines have encountered.
R21 comes on the heels of the pioneering RTS,S vaccine, which received WHO approval in October 2021. The 4-dose vaccine has shown to reduce severe malaria by at least 30% and has already been administered to millions of children. When administered at full scale, this vaccine can save tens of thousands of lives annually. Still, multiple efficacious vaccines are needed, as part of a larger malaria prevention landscape, to reach millions of at-risk children each year and make significant strides towards eradication.
I spoke with Dr. Mehreen Datoo, Clinical Research Fellow at the University of Oxford’s Jenner Institute. You can watch the film and read the full interview below.
Emile Dawisha: Why is the R21 vaccine a gamechanger in the fight against malaria?
Dr. Datoo: R21 is a game changer because it’s a high-efficacy vaccine targeting the youngest and most vulnerable children. Our partnership with the Serum Institute of India means that it can be manufactured at large scale and low cost to ensure it can reach as many children as possible and have a significant impact on them and their families in the long term living in malaria endemic areas.
Mr. Dawisha: How long has this vaccine been in development? Tell us about the various stages of testing it’s been through, and your role in its development.
Dr. Datoo: R21 was first produced, I think, shy of 10 to 12 years ago in [the University of] Oxford. Obviously it went through all its pre-clinical trials and testing. And then I came in basically to lead the clinical development program of R21/Matrix-M™. And this is when it basically was starting its Phase I and Phase II trials by the project made by the Serum Institute of India.
So prior to this, R21 was manufactured in [the University of] Oxford, at a very small scale. Some initial trials were done that showed potential high efficacy, and therefore manufacturing transferred to the Serum Institute of India. The vaccine was made, and we then initiated the first in-human Phase 1 trials here in [the University of] Oxford. And following good results with that, we did a Phase 2a challenge study, so that’s why we used the controlled human malaria infection model to basically check if the vaccine works in malaria-naive participants, i.e. adults in the UK.
Because we got good results with that, we then obviously wanted to then test it in a malaria-endemic area because we know that vaccines work differently between malaria-endemic and malaria-naive people. So we did our Phase 1 in Kenya – it was at our Kilifi institute in Kenya – where we basically, that was the first testing of R21 in a malaria-endemic area. And we basically looked at the safety of the vaccine and how the immune response to the vaccine worked, in adults, young children aged 1-5 and infants aged 5-12 months.
The vaccine was safe, it was well tolerated. And so, following that, we started our Phase 2b trials in Nanoro, Burkina Faso, which enrolled 450 infants age 5 to 17 months. They were randomized basically to receive a malaria vaccine or a control rabies vaccine. And there we looked at field efficacy, and we measured at 12 months following the primary series of vaccinations, and 12 months following a booster vaccination. And we’ve actually even been testing additional booster vaccination. So these participants are all due to complete their 4-year follow-up imminently actually, in June this year.
Our primary series of vaccinations is three vaccines, four weeks apart, and we aim to give a boost a year later.
Because of the good results seen in the Phase 2 trial, that’s why we started our Phase 3 trial. And we are in the second year of follow-up actually with our Phase 3 trial. So our Phase 3 trial is looking at a wider age group. So that’s 5 to 36 month old participants, because we do know that actually two-thirds of [malaria] deaths are in children under-5, so we want to encompass as much of the age group as possible.
With our Phase 2 trial, we had tested what we call seasonal administration, because it was in an area of highly seasonal malaria transmission. So we administered the primary series of vaccinations prior to the malaria season and the booster prior to the malaria season. So therefore for the Phase 3, we expanded it to areas of different malaria transmission, so seasonal transmission, but also perennial transmission, so transmission all year round in high and low areas. So our countries for the Phase 3 trial are Burkina Faso, Mali, Tanzania, and Kenya. And as I said, all our participants have had a booster a year later after their primary series of vaccinations and we’re in second year of follow-up.
Mr. Dawisha: What is the long-term goal of R21 and what are the roadblocks to achieving that goal?
Dr. Datoo: So we know that progress in combatting malaria has stalled. But we really hope that R21 will be a valuable part of the toolkit contributing to elimination and eradication of malaria.
In terms of thinking about our challenges, we set up our Phase 2b trial, and our Phase 3 trial was ongoing, at the height of the COVID-19 pandemic. But actually we have been very fortunate; our local site teams in Africa have been excellent. Hats off to them. They have got the trial started, ran the trial, managed the trial, and have kept everything going through all these difficulties to now show our successful results. So we are extremely grateful to everyone who has helped in this effort, working with us on this trial.
In terms of now where we are going, we are in the process of working towards all the requirements with the WHO for policy recommendation and pre-qualification to help facilitate widespread deployment as soon as possible. And we are discussing with the national regulatory authorities in Africa for in-country approvals also. As discussed, we were very pleased to recently receive approval for use in Ghana and Nigeria.
We know that progress in combatting malaria has stalled. We know R21 is a high-efficacy vaccine that works really well in the youngest and most vulnerable children. The reason we think this is really important is because, as progress has stalled, it is really important that something new and innovative comes to try and help the situation because it’s having such an impact on their lives and families.
And that’s why we had worked with the Serum Institute of India, because we do know that it’s really important to have as much vaccine as possible, for large-scale manufacturing and also for low cost, so it can actually reach all the children that it needs to.
When you think about the number of children in Africa, we do need – and it’s a 4-dose vaccine – we do need to ensure that we do have sufficient supply. And that’s why I think R21 is really important to, you know, be deployed as soon as possible, pending all the approvals, obviously.
Stay tuned as we highlight a new Malaria Gamechanger each week throughout May!