The world at last has a public health tool it has been seeking for more than a century: a reliable vaccine against malaria that can protect at least two-thirds of the children who receive it from developing the deadly disease.
In fact, in an embarrassment of riches, the world now has two. Last week, the World Health Organization gave its recommendation to a vaccine formula called R21/Matrix-M, developed by the University of Oxford and the Serum Institute of India, following preprint publication of Phase 3 results that showed 68 to 75 percent efficacy. (The study has not yet been peer-reviewed.) That comes just three months after the rollout of a separate vaccine called RTS,S/AS01, developed by GlaxoSmithKline, which achieved 55 percent efficacy. The WHO approved that formula in October 2021.
The RTS,S vaccine is beginning to be distributed in 12 African nations. After some regulatory steps, the R21 vaccine is expected to debut next year. Together, they could make an extraordinary difference in the survival of children in tropical countries—though experts say it is far too soon to abandon traditional tools, such as bed nets, that have kept malaria imperfectly suppressed until now.
“Up to 620,000 people die of malaria every year. It’s a huge economic burden on countries,” says Lisa Stockdale, a senior immunologist in the University of Oxford’s Jenner Institute and a member of the R21 research team. “If we can get everyone vaccinated, this has enormous potential to save lives.”
Achieving an effective vaccine has taken so long because malaria is a uniquely wily foe. The disease is caused by a parasite that is something of a shape-shifter. It enters the body through the bite of a mosquito. It migrates into the liver, multiplies there, and then moves into the circulatory system’s red blood cells. In each of those stages, it takes on a different form and produces thousands of different proteins. Interfering with this multi-stage infection is a complex maneuver, far more challenging than teaching the body to protect itself against viruses or bacteria.
“Vaccines provide information to the immune system so the immune system can learn about a pathogen,” says Steve Taylor, an infectious disease physician and associate professor at the Duke University School of Medicine who studies malaria. “A virus contains as much information as a pamphlet; you can provide its essence to the immune system quickly. But we have many fewer vaccines against bacteria, because they are more complex—like a nonfiction book. And malaria parasites are like a 1,000-page novel.”
The strategy used by both new vaccines aims to overcome the parasite as it enters the body and before it hides in the liver to reproduce. At that point, it has made few copies of itself and is in a relatively uncomplicated form. Both vaccines make use of manufactured assemblages of circumsporozoite protein, or CSP for short—which the parasite expresses in that early stage—to teach the immune system to recognize the parasite and overcome it.
Both vaccines are meant to be given to infants via a three-dose series, then topped off by a booster a year later. They appear to protect children for years, although that protection is not expected to be lifelong. The older vaccine has not been deployed long enough for anyone to predict its durability, and the newer one remains in clinical trials.
The number of shots needed to protect a single child makes it clear how many doses will be needed. So far, 1.7 million children in three countries have received almost 5 million doses of the RTS,S vaccine through a pilot program. Now 18 million doses of that vaccine are being made available in a three-year allocation cycle. Yet the WHO has estimated that annual demand for both vaccines will be 40 million to 60 million doses per year to begin with, and could rise to as many as 100 million by 2030.
GSK, which developed RTS,S (now called Mosquirix), plans to transfer it to the Indian pharma company Bharat Biotech, a move that could increase manufacturing capacity. And once it comes into production, the newly recommended R21 could add 100 million doses to the total available, according to the Serum Institute of India, which is serving as its manufacturing partner. For that to happen, the WHO still needs to prequalify the vaccine, an assessment that tells nonprofit purchasers and national regulatory authorities that a new drug is safe and effective. Though no date has been set, prequalification is expected soon, with a goal of beginning distribution next year.
At that point, a delicate dance will begin. The agencies and nongovernmental organizations that ensure vaccine availability for low-income countries will need to stimulate enough production from enough manufacturers to avoid the kind of competition that kept the earliest batches of Covid vaccines from reaching poorer nations. Meanwhile, they will be trying to build production capacity in the countries where the vaccine is most needed.
Though homegrown malaria recently flared in the US, “there’s no high-income market for this product,” says Aurélia Nguyen, the chief program officer of Gavi, the Vaccine Alliance, which has made an initial commitment of $155 million to bring the new formulas to market and is beginning work on what it calls an African vaccine manufacturer accelerator. “Let’s make sure we really optimize the two suppliers we have today. But over time, let’s make sure we build toward a diverse manufacturer base, including diversity in terms of geographic production.”
For now, experts say the arrival of the vaccines won’t mean that countries can stop using long-standing methods of controlling malaria: spraying insecticides, distributing treated bed nets, and ensuring that people receive affordable preventive drugs. Sustained promotion of those methods by international agencies since 2000 has forced malaria rates down, but that progress has stalled recently. So the vaccines are urgently needed—but at this stage, they can’t be considered a replacement.
“The vaccines focus on children under 5, so they don’t cover the entire population. The other interventions do,” says Michael Adekunle Charles, a physician who is CEO of the nonprofit RBM Partnership to End Malaria. “And their efficacy is not at 100 percent. So in order to really get the coverage that is needed, we need to combine it with other tools to get the maximum benefit.”
As the vaccines roll out, they will also face the hurdles that other campaigns have encountered: challenges in distributing doses to remote areas, keeping them within safe temperature limits, and ensuring that health care workers and parents will be enthusiastic about their arrival. But the biggest hurdle—as always, in global public health—will be money. Keeping up donor zeal, from philanthropy and from rich nations, has been a long-time challenge for multiyear vaccination campaigns such as those against measles and polio.
Supporters hope the vaccine can make the case on economic benefits, not just on humanitarian grounds. In some low-income countries, malaria prevention consumes 40 percent of health care budgets. The cost to global productivity is believed to be $12 billion per year. Currently, though, “malaria funding is not looking good,” Charles says. “We have 50 percent of the funding we need, a $3.6 billion shortfall every year. The mosquito is consistently evolving—and if we don’t get ahead of it, the mosquito will continuously outsmart us.”
