Malaria expert Brian Greenwood had once resigned himself to the possibility that a successful vaccine for the disease might not become available in his lifetime. Now, at 86 years old, the moment he’s spent four decades working toward has arrived.
“It’s been a long journey with many ups and downs,” says Greenwood, still an active researcher at the Royal Society of Tropical Medicine and Hygiene, leading vaccine trials across Africa. “The first attempts to develop a malaria vaccine through studies in birds were done over 100 years ago.”
Beginning today, Cameroon, a Central African nation which experiences 2.7 million cases of the disease each year, will start rolling out the world's first routine childhood malaria immunizations using a vaccine called RTS,S or Mosquirix, made by the pharma company GlaxoSmithKline. The vaccine targets sporozoites, the transmissible forms of the malaria parasite, and neutralizes them before they can enter the liver and multiply in their thousands.
With 48 percent of all hospital admissions and 67 percent of childhood deaths in Cameroon linked to malaria, the hope is that this new rollout will help relieve the considerable burden the disease places on the country’s health care system.
“The impact of this vaccine goes beyond the medical benefits examined in clinical trials,” says Mohammed Abdulaziz, head of disease control and prevention at Africa CDC. “Malaria is a major reason for school absenteeism, anemia, and impaired cognitive development. This vaccine can help break the cycle of adversity plaguing our youth for a long time.”
Despite efforts to eradicate mosquitos carrying the Plasmodium falciparum parasite—the deadliest source of malaria on the African continent—and the use of protective nets and coating the walls of houses with insecticides, malaria still killed 608,000 people in 2022. Ninety-five percent of the fatalities were in Africa; young children, whose immune systems are still developing, are by far the most vulnerable. According to the charity UNICEF, a child under 5 dies of malaria nearly every minute.
The rollout is expected to expand swiftly. Twelve African countries will receive a combined total of 18 million doses of RTS,S over the next two years through Gavi, the vaccine alliance that ensures immunization access in some of the world’s poorest nations. Cameroon will receive 662,000 doses in 2024, with Burkina Faso, Sierra Leone, Benin, and others set to follow. All the vaccines so far are earmarked for children due to availability constraints.
“We have more than 30 African countries today who have expressed interest in a routine malaria vaccination program,” says Aurélia Nguyen, chief program officer at Gavi.
The vaccine will undoubtedly save lives. In October, the World Health Organization announced that a previous pilot rollout of RTS,S in hundreds of thousands of children across Ghana, Kenya, and Malawi over four years had reduced deaths by 13 percent and severe cases by 22 percent.
But a perceived lack of urgency has already received criticism. The efficacy of RTS,S was first demonstrated in clinical trials as far back as 1998, yet the WHO did not officially recommend its use until 2021. More than 18 million people, mainly children, are thought to have died of the disease since those initial trials.
There’s also the question of how many children living in high-risk areas will actually receive the new vaccine. While GSK committed to producing up to 15 million doses of RTS,S per year through 2028, following the start of the WHO-backed pilot program in 2019, this will only be sufficient to benefit a small fraction of those who need them. With approximately 200 million school-age children at risk of the disease throughout Africa, experts say that difficult decisions have been made about which countries and regions should be initially prioritized.
“Coverage is not going to be as widespread as we’d like,” says Jaishree Raman, who runs a malaria research lab at the South African National Institute for Communicable Diseases. “They’ve had to make hard decisions. There will be regions which still have a high burden of malaria, which will miss out.”
An estimated 100 million vaccine doses every year will be needed by 2030 in order to control malaria in areas where the prevalence is highest. A second malaria vaccine called R21, developed by scientists at the University of Oxford, may help make up the shortfall.
The WHO added R21 to a list of prequalified vaccines last month, following studies which showed it reduced symptomatic cases of malaria by 75 percent in the 12 months following a three-dose series. At a cost of $2 and $4 per dose, it’s approximately half the price of RTS,S, and the production capacity is far greater. This is due to a partnership which has been struck between the Oxford scientists and the Serum Institute of India, the world’s largest vaccine manufacturer.
“They produce half of all vaccines in the world, and they can rapidly increase their production rate,” says Greenwood. “GSK has done all the groundwork with RTS,S which R21 has benefited from. But the Serum Institute have said they could produce over 100 million doses a year fairly quickly.”
According to Nguyen, R21 will start to become available in either May or June 2024. Numerous logistical hurdles lie ahead, including the notorious “cold chain,” the strict refrigeration requirements of vaccines that inhibit how easily they can be transported to remote regions and stored.
“Even if all the vaccines were there, you couldn’t just suddenly say, ‘Well we’ll vaccinate the whole of Ghana’ straight away, because you need enough cold storage, staff, and so on,” says Greenwood.
Another challenge will be the number of required doses for each patient. WHO guidelines state that both RTS,S and R21 should be administered in a schedule of four doses in children from around five months of age, with an optional fifth booster dose to be given a year later.
“For me that’s one of the biggest concerns,” says Raman. “In the trials they had very good coverage, but there were people closely documenting it, and I don’t think that’s going to happen in a real-life setting.”
Another open question is the long-term durability of both jabs. Greenwood says that ideally all children living in high-risk areas would be boosted on an annual basis until the age of 10. While the WHO reports both RTS,S and R21 as being 75 percent efficient at preventing clinical malaria when given seasonally alongside antimalarial tablets, previous trials have illustrated how quickly immunity can wane over time. A study published in 2015 showed that RTS,S only had 36.3 percent efficacy an average of four years after toddlers were vaccinated. Plasmodium falciparum is also only one of five different parasite species which cause malaria; the vaccination campaign may cause it to evolve in a similar manner to many viruses, or another malaria parasite may become dominant in Africa.
However, the biggest challenge of all is funding. Raman is concerned about the current overreliance on foreign donors such as Gavi and UNICEF to provide vaccine supplies. “A lot of the malaria control programs across Africa depend largely on donor funding,” she says. “But there needs to be more domestic funding. Donors are never going to be around forever, and they do change priorities, which has huge consequences for disease control programs.”
Efforts are already underway to address this by at least shifting some of the burden of vaccine production to Africa. Abdulaziz says that Africa CDC is working on improving manufacturing facilities across the continent, while the Serum Institute is reportedly in discussions with manufacturers in Nigeria and Ghana to discuss a tech transfer which would enable R21 to be produced in those countries.
It may not be long before other malaria vaccines start to become available, with BioNTech initiating a program to develop a mRNA vaccine for the disease, and Maryland-based biotech Sanaria also developing a jab.
Greenwood is hopeful that further progress will yield cheap vaccines that require fewer doses and remain efficacious for longer, enabling vaccination coverage to be widened and possibly even expanded to other parts of the world.
“There’s a lot going on,” says Greenwood. “I think we’ll have other vaccines in a few years. If a vaccine was really cheap and available, you might think about using it in other groups, for example agricultural workers or people going into the forest.”
As imperfect a solution as it may be, the rollout of RTS,S does represent a significant new dawn in the battle to save children’s lives from malaria across the African continent.
“For a long time, we have been waiting for a day like this,” says Abdulaziz. “The vaccine brings more than just hope.”