Is new malaria vaccine ‘world-changing’? Maybe.

Dyann Wirth-Big 3

September 28, 2022 – A new vaccine for malaria developed by scientists at the University of Oxford was up to 80% effective at preventing disease in young children, according to trial results published in early September. Dyann Wirth, Richard Pearson Strong Professor of Infectious Diseases, offers some thoughts on the new vaccine and its potential impact.

Q: Media reports have suggested that the new vaccine could be “world-changing.” As someone who has studied malaria for years, do you have a similar level of excitement?

A: Whether it will be world-changing, we’ll have to wait and see, because so far there has only been early testing of its efficacy.

This new vaccine, called R21, is potentially an improved version of another vaccine, called RTS,S, which the World Health Organization approved last October for broad use in regions with significant malaria transmission. RTS,S was the first-ever vaccine for a human parasitic infection.

RTS,S also showed high efficacy in limited samples in early testing, but once it was deployed in a more real-world setting—in Phase 3 clinical trials—both the predicted and observed efficacy were down closer to 40%-50%, and they’ve stayed that way. It turns out that when you give the vaccine, relative to the transmission season, affects its efficacy. In many countries, malaria spread typically peaks during the rainy season, when there is more stagnant water in which mosquitoes can breed. A recent study from Brian Greenwood of the London School of Hygiene and Tropical Medicine and colleagues found that an RTS,S shot given directly before transmission season in West Africa had extremely high efficacy.

For R21, only 450 children aged 5-17 months, a small number, were included in the recent trial conducted in Burkina Faso, where malaria infections are seasonal. The study showed that three initial doses of the vaccine, followed by a booster a year later, was up to 80% effective at preventing infection.

I would say that we need to evaluate R21 under more real-world settings, including the Phase 3 clinical trial, which began in April 2021 and runs through December 2023, and includes 4,800 children in four African countries, including two where malaria is a threat throughout the year. I’m optimistic about the new vaccine, but I also recognize that early data is often more promising than when things are actually used in practice.

Q: How important is it to have this new, hopefully effective vaccine?

A: The overall worldwide demand for this vaccine could be up to or over 100 million doses per year. As we now know from the experience with the coronavirus, having more than one source of vaccine is crucial to withstand potential disruptions in supply chains, problems with quality control, or other issues.

After the WHO recommended the broad use of RTS,S last October, I think it caused a paradigm shift. There’s now significant new effort in developing malaria vaccines. BioNTech, one of the developers of the mRNA-based coronavirus vaccine, wants to develop an mRNA-based vaccine for malaria, and there will be clinical trials for that soon. There’s also a very large program, funded by the Gates Foundation, to use monoclonal antibodies as a preventative tool against malaria. I think all of the excitement and development in this arena is great, given the reality that there are 280 million cases of malaria every year and nearly half a million deaths of children.

In addition to vaccines, the other two main approaches we have for fighting malaria are vector control—essentially preventing the mosquito from biting the human, either by killing the mosquito or by using bed nets treated with insecticide—and diagnosis and treatment with antimalarial drugs. However, drug resistance is a problem.

There’s an enormous need for new approaches to fight malaria because microorganisms like the malaria parasite have various ways of escaping being killed. Evasion is a common feature. We’ve seen a similar scenario with the coronavirus, where variation in the virus has essentially reduced the efficacy of previous immunity either induced by the vaccine or by getting the disease. I think this is also true in malaria. Data has shown that there is strain-specific protection, very much like we’re seeing with the coronavirus. With these microorganisms that are struggling for survival, such as the malaria parasite, I think we need to be less naïve about thinking there’s going to be a magic bullet. We will continue to need other tools and additional vaccines.

Q: One expert was quoted in the press as saying that the development of the new vaccine suggests that it may be possible to end child deaths from malaria in our lifetimes. What do you think?

A: I hope that’s true. This is a preventable, treatable disease. No child should die of this.

The reality is that, between roughly 2005 and 2015, childhood deaths from malaria were halved by better implementation of bed nets and diagnosis and treatment. And then things kind of plateaued. A vaccine, which is a completely different strategy, could have an impact if it’s used cleverly, by vaccinating or boosting right before the rainy season to get the maximum effect, while also using the other tools in our armamentarium. I’m very excited about the potential that by using a multi-pronged strategy we could have a dramatic impact.

Karen Feldscher