Ashley Birkett, PhD, leads PATH’s efforts to develop and introduce safe and effective vaccines and monoclonal antibodies for the fight against malaria. Seven months since the World Health Organization’s (WHO’s) recommendation and five months since Gavi’s decision to help fund the introduction of RTS,S/AS01 (RTS,S) in countries, Ashley answers questions on the world’s first malaria vaccine and how it is informing PATH’s work on the next generation of vaccines and biologics.
1. Ashley, why is it so important to develop and introduce vaccines against malaria?
Progress in controlling malaria has stalled. Actually, there is a reversal of progress in some high-burden countries. To get back on track, the global malaria community has a two-pronged approach: use the tools we already have more effectively and develop new tools.
I think a vaccine has potential for high impact. This thinking is driven in part by the fact that we already have effective ways to deliver vaccines to young children in Africa. Even in some of the poorest regions of Africa, where malaria is a huge problem, we see very high coverage with vaccines.
We have seen evidence of this in the ongoing pilot implementation of the RTS,S malaria vaccine in Kenya, Ghana, and Malawi. Importantly, the vaccine is expanding the reach of malaria prevention tools by reaching some children who are not using other forms of malaria prevention, such as long-lasting insecticide-treated nets. This means we are going from reaching 60 or 70 percent of kids with nets to reaching around 90 percent of children with either a net, the vaccine, or both.
2. What is the current landscape for vaccines against malaria?
We have to start with the RTS,S vaccine. In 2021, WHO recommended widespread use of the world’s first malaria vaccine, which is also the first vaccine against a parasite in humans and the first new malaria tool recommended by WHO against malaria in about a decade.
It will be important for us to maximize the impact of RTS,S—what we’re calling a first-generation vaccine—but we're going to need more than one malaria vaccine because the market is expected to be quite large. This market would be better supported by multiple manufacturers, which is one reason we have high hopes for the R21 malaria vaccine candidate, which is currently in Phase 3 clinical trials. Based on current data, R21 seems to have similar characteristics to RTS,S.
3. Why is there value in having more than one vaccine available?
There are several reasons. First, if you only have one supplier, and if that supply runs into manufacturing difficulties for whatever reason, you risk the supply of the malaria vaccine.
Second is economics. If you have multiple suppliers, you drive competition, which is better for the consumer, as it can impact the price of the vaccine. Competition should also drive innovation, as manufacturers seek to preserve or grow their market share by offering vaccines with superior performance.
Lastly, according to a WHO market study, the projected market for malaria vaccines is approximately 110 million doses per year by 2036, which is quite large. And, typically, that’s a market that wouldn’t be served effectively by a single manufacturer.
4. PATH has played a key role in the development and introduction of the RTS,S malaria vaccine. What are you doing now to maximize its impact?
We are helping to accelerate the introduction of RTS,S into more areas of Ghana, Kenya, and Malawi—the three countries participating in the pilot implementation of the malaria vaccine—through funding from Open Philanthropy. This recently announced award for $5 million will allow pilot countries to more quickly expand access to the vaccine.
We’re also working to ensure that the anticipated gap between supply and demand for malaria vaccines is minimized, including by scaling up production of RTS,S and other approaches that could improve coverage, such as fractional dosing.
At the same time, we’re supporting research to continue learning how best to use and deploy the RTS,S vaccine, particularly in highly seasonal malaria settings. In these settings, we have learned that if we target immunization to align with the peak transmission season, and combine vaccination with seasonal malaria drugs, it can have quite profound effects.
5. Can you explain what is meant by “next-generation” vaccines, and why the world needs them?
First-generation vaccines are those that are going to have similar performance characteristics to RTS,S: modest efficacy, relatively short durability, and require several doses. When we think of next-generation vaccines, we are aiming to move the needle on at least one of those parameters, such as increased durability of protection.
Those next-generation vaccines are maybe five or even ten years away. Given the current uncertainty on how best to achieve this goal, we support two pathways: one is to improve current vaccines, which would effectively leverage the investments in scaling up production of RTS,S that we anticipate over the coming years, and the other is to create new vaccines. We think there needs to be parallel investment into both pathways until we have more assurance on which approach will work.
6. Is PATH working on any next-generation vaccines?
We're working on a range of next-generation vaccines with multiple partners and with support from multiple donors. We’re also working on monoclonal antibodies, an innovative tool with potential to offer high-level protection against infection and onward transmission.
Our work spans all stages of the Plasmodium parasite’s complex life cycle. These include vaccines targeting the same protein as RTS,S to stop the parasite from entering the blood stream by targeting it before it exits the liver, approaches to combatting the parasite when it reaches the blood stream, vaccines to block transmission of the parasite from humans to mosquitoes, and finally, combination vaccines targeting multiple life cycle stages.
7. Has the rapid development of COVID-19 vaccines changed how you think about future malaria vaccine development?
I think it has. It’s challenged the status quo in terms of vaccine development and introduction timelines for other diseases. In much of the world, particularly in wealthy countries, we have viewed COVID-19 as a public health emergency. However, if you’re a mother of a child in most of Africa, where nearly 500,000 young children continue to die every year, malaria is the public health crisis that concerns you most. We have to change mindsets. It’s time to start addressing malaria with the same urgency as COVID-19.
8. Tell us about your team’s work on monoclonal antibodies. How could they help prevent malaria transmission?
One of the potential benefits of monoclonal antibodies is that they could be given as a single shot, and primarily before periods of risk during times of high transmission. In highly seasonal settings, where most of the malaria occurs over four to five months, the idea is that you could get a single monoclonal antibody shot just before the malaria season, and it would protect you through the whole season.
Compared to vaccines, monoclonal antibodies also could potentially have higher efficacy. We all respond differently to vaccines, but with monoclonals, you’re taking out that variable because you’re just putting the agent (the antibody) in the body directly instead of asking your body to develop it.
Monoclonal antibodies for malaria are in clinical trials in sub-Saharan Africa. The initial proof-of-concept studies are looking very encouraging. However, the challenges now are to translate this promising research into products that work in real-world settings, can be delivered effectively, are accepted by the communities that could benefit from them, and be affordable.
9. Looking ahead, what excites you the most about your work?
I’d have to refer back to the WHO recommendation for widespread use of the first malaria vaccine in 2021, which showed that it can be done. It was a long journey and a lot of trailblazing, but the first vaccine is here, and it’s starting to have impact and save lives.
This achievement is very important not only in the context of this first malaria vaccine but also for what it means for future malaria vaccines: the learnings and the opportunity to move faster to impact, in terms of challenging the status quo on development and introduction timelines.