Vaccinating against malaria has posed a real challenge for scientists for decades. But the tide may be turning.
Every year, malaria kills more than 400,000 people, most of them children. There has been significant progress against the disease in the past few decades — death rates have fallen nearly in half since 2000 — but there’s still a long way to go.
For decades, researchers have been working on developing a vaccine. It hasn’t been easy. Malaria, a parasite infection, is hard to vaccinate against, and many attempted vaccines haven’t produced durable immunity.
But progress is happening. On Wednesday, the World Health Organization (WHO) announced it has given its stamp of approval to a vaccine against malaria for children for the first time, after encouraging results from a pilot study that has reached hundreds of thousands of children across parts of sub-Saharan Africa since 2019. The vaccine, called Mosquirix and made by GlaxoSmithKline, is far from perfect — it produces about a 30 percent reduction in severe malaria in fully vaccinated children, which is lifesaving but smaller than would be hoped for.
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But the WHO recommendation is a step forward in the fight against one of humanity’s deadliest remaining infectious disease enemies. It will likely lead to countries adding the vaccine to their childhood immunization programs starting immediately. And it’s only the first step of many to come. Researchers are already working to improve on Mosquirix, and with a combination of different approaches, it might be possible for the world to significantly cut down on malaria’s staggering human toll for good.
“This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health, and malaria control,” WHO Director-General Tedros Adhanom Ghebreyesus said.
The malaria fight, explained
Malaria is a mosquito-borne disease that causes fever and chills, and in severe cases anemia, seizures, and respiratory problems. With treatment, it’s very rarely fatal. Nonetheless, it is estimated that the approximately 220 million cases of malaria each year cause about 400,000 deaths. Even preventing 40 percent of cases saves many lives, and since part of the malaria parasite’s life cycle is inside a human host, disrupting some cases will benefit even the people who are not conferred immunity.
Researchers have been working for more than 30 years on the line of research that led to this malaria vaccine. While widespread use of insecticide-treated bednets, preventive treatment, and indoor spraying have driven malaria deaths down significantly since 2000, the gains from those approaches have been flattening in recent years.
Continued progress against malaria is going to require new tools in the toolbox — and Mosquirix, also known as RTS,S, looks like a promising one.
In clinical trials, the vaccine prevented about 40 percent of cases of malaria, and 30 percent of the most severe cases. That’s much, much lower than the success rate of vaccines for most other early childhood diseases. The measles vaccine, by comparison, is 97 percent effective, and the chickenpox vaccine prevents 85 percent of cases and nearly 100 percent of severe cases.
But with malaria killing hundreds of thousands of people every year, even a partially effective vaccine can be a lifesaver for many, many people. Recent research modeling the effects of a widespread Mosquirix rollout estimates that “5.3 million cases and 24,000 deaths could be averted” if we’re able to get the vaccine to the 30 million people at the greatest risk annually.
Evidence from the pilot rollout in Malawi also suggests that the vaccine works well in combination with existing malaria-fighting options like the distribution of malaria-preventing drugs to children in high-risk areas. That’s important, because the vaccine isn’t sufficient on its own.
“Many global health organizations have worked long and hard to make an efficacious malaria vaccine a reality. There’s still an imperative to sustain existing interventions alongside, so we’ll be looking for donors to up their total contributions to fight against malaria to incorporate this new tool into their armaments,” Amanda Glassman, the executive vice president at the Center for Global Development, said in a statement.
The vaccine is administered as a series of four shots — three a month apart, and then a fourth a year later — and the effectiveness of further booster shots is being tested. With more than 2 million shots administered in the pilot programs to date, very few serious side effects have been reported, so the vaccine’s safety profile looks good. The vaccine is also relatively cost-effective, costing about $5 a dose.
The WHO approval does not, by itself, ensure widespread vaccine access. Instead, now that the organization has made its recommendation, the next steps are “funding decisions from the global health community for broader rollout, and country decision-making on whether to adopt the vaccine as part of national malaria control strategies,” the WHO says.
But many countries follow WHO recommendations in setting their national health policy, and the recommendation is expected to spur countries to add this vaccine to their anti-malaria toolbox. And the WHO announcement will hopefully also spur funders to step up and help pay for ensuring the vaccine reaches everyone who needs it.
Why it’s hard to vaccinate against malaria
The Plasmodium parasite that causes malaria in humans needs both blood-sucking insects and humans for its life cycle. It grows inside a mosquito and is transferred to a human host when the mosquito bites them. Then the parasite migrates to the liver, replicates itself, and infects the blood — where it can be taken up by the bite of another mosquito.
When the parasite is in the blood, it causes fever, chills, and flu-like illness. Healthy adults usually recover, but those with a weaker immune system — especially young children and pregnant people — can die. In addition, it’s also one of the leading causes of miscarriages and stillbirths in the world.
(Older people who live in regions where malaria is endemic are, surprisingly, not especially vulnerable. The theory is that after sufficient exposure to malaria over a lifetime, the immune system develops a general anti-parasite response that might be more durable than malaria-specific immunity.)
In rich countries, malaria was largely eradicated in the mid-20th century through mass spraying of insecticides, including ones like DDT that have since been banned due to their ecological consequences. But many poor countries still have endemic malaria, and the range of malarial mosquitos is expanding due to climate change.
Vaccinating against malaria is tricky. Parasites are much more complex than viruses, with many possible sites that the immune system might be trained to recognize.
“Malaria vaccine [development] has been a graveyard for really great ideas,” Derek Lowe, a researcher who writes about drug discovery, told me earlier this year. “We’ve learned about a lot of stuff that doesn’t work.”
Targeting the parasite once it’s in the blood, for example, has been tried repeatedly but has never succeeded.
Exposing the body to dead or neutralized Plasmodium? A dead end. Researchers have been working on this for decades, and progress has been rare.
The earliest success stories of vaccination involved vaccines against diseases that produce lifelong immunity, like smallpox and polio. Those are viruses, so they’re much simpler to target. And since you can’t be reinfected with those diseases, the vaccine only needs to provoke the same immune response as the disease did originally, and the patient is safe for life.
But in the case of malaria, naturally acquired immunity against it typically is only partial and fades out in a few years. Researchers have been working for decades to figure out how a vaccine can induce durable immunity, and most of that work has ended in frustrating failures.
That’s now changing. Mosquirix is the first vaccine to get promising results, but other vaccines have actually shown even higher efficacy in early trials. A recent phase 2 clinical trial of a malaria vaccine called R21/MM found 77 percent efficacy — a big step up, if it holds up in larger-scale trials.
And with many other vaccine candidates making their way through trials, these two early vaccines are likely to be joined by others.
The progress of malaria vaccine candidates is a story that’s rarely in the headlines but is big news for the world. Lessening the burden of this deadly disease for millions of people will save and improve a lot of lives. Vaccination is one of our most powerful tools against infectious disease, and our recent successes at bringing it to bear on one of our deadliest enemies is a triumph worth celebrating.
