The trials and tribulations of the world's first malaria vaccine

ACCRA, Ghana — At Tuobodom Health Centre, a few hours north of Kumasi, Ghana, 7-month-old Rejoice sits happily on her mother’s lap, playing with an empty syringe wrapper as a community health nurse prepares her second shot of the world’s first malaria vaccine.

Having talked over the potential side effects with the baby’s mother, Augustine Tamia, the nurse swiftly injects it into a chubby thigh.

Developed by GlaxoSmithKline, the vaccine — known as RTS,S — has been shown in clinical trials to reduce a child’s chance of contracting malaria, which is one of the world’s biggest killers of children, by 40%. It is currently undergoing pilots in Ghana, Kenya, and Malawi.

For Tamia, giving Rejoice the vaccine was a simple decision. Philip, her son, suffers from regular bouts of malaria that leave him weak from vomiting and diarrhea and prevent him from attending school for weeks at a time. Paying for his antimalarial drugs means extra hours working in the cassava fields, a job that has already cost Tamia the tip of one of her fingers. The 29-year-old mother is desperate not to see Rejoice go through the same, she told Devex — if there is an injection that can help, she is happy for her daughter to receive it.

The four-year pilot, coordinated by the World Health Organization, started in 2019 to establish the feasibility and safety of the vaccine in local health contexts. If successful, RTS,S could be rolled out globally to help tackle Plasmodium falciparum, the deadliest malaria parasite, which is most commonly found in Africa.

However, things have not always gone smoothly for the vaccine, which has been in development for 30 years. Trials suggest it provides only partial protection against malaria, preventing 4 out of 10 cases — though it also lessens the severity of cases that do occur — and its efficacy wears off four years after the final dose.

That’s still a good result considering the complexity of the disease, experts say. But the pilot has also faced challenges, including from the growing anti-vaccination movement, and claims from some in the medical community that parents are not being given the full picture about potential risks. Are such problems enough to derail this long-awaited vaccine?

Anything helps

Despite impressive global results in the fight against malaria, some parts of the world have seen worrying increases in cases in recent years. The spikes are linked to mosquito and parasite resistance to insecticides and antimalarials, as well as changes in land use, demography, and climate that can affect malaria transmission.

As a result, the vaccine has been welcomed in Ghana, despite its shortcomings. “Malaria is the biggest problem we have … [and] the biggest cause of hospitalizations. … If we are able to prevent 40% of malaria [cases], that is significant,” said Dr. Samuel Harrison, a fellow at Kintampo Health Research Centre, which is helping to evaluate the pilot in Ghana.

The center’s director, Dr. Kwaku Poku Asante, pointed out that other vaccines, such as for tuberculosis, also have relatively low efficacy rates.

However, the vaccine must be seen as an addition to — rather than a replacement for — existing malaria interventions. Evaluators are monitoring how the vaccine impacts the use of other prevention methods. “We don’t want to shift the focus of malaria control from spraying houses and use of bed nets to just the vaccine,” Asante said.

Another worry is the feasibility of giving the vaccine in four doses spread over two years, starting at 6 months of age and separate from the routine immunization schedule. Experts are concerned that parents may struggle to bring their children for all four doses or may skip the last ones if they think the vaccine is already working.

At Tuobodom Health Centre, where Tamia brings Rejoice for her shots, only about 5% of mothers miss appointments, and these are tracked down by staff, said Irene Asare Danko, a community health nurse.

Furthermore, even with four doses, a vaccine is still by far the most convenient preventive measure for parents and children, according to Keziah Malm, director of Ghana’s National Malaria Control Programme. “It is easier for people to accept the preventive intervention that requires less of their action and behavior change,” she said.

Questions about consent

Vaccine hesitancy threatens the pilot as well. In its early stages, social media videos circulated saying that Ghanaians were being used as “guinea pigs” by a foreign pharmaceutical company and that the injections caused infertility.

“When [the vaccine] first came out, some people didn’t want it … because they’d heard on social media and TV that it will make [the baby] infertile, but we educated them,” Asare Danko said.

Asante agreed that misinformation about the vaccine had been an issue but said the fact that 100,000 doses had already been administered showed that “acceptability is high.”

More recently, the pilot has been criticized by some over its consent policy. An article in The BMJ said that parents are not being properly informed about the vaccine’s potential side effects, which include increased risks of meningitis and cerebral malaria. The author, Peter Doshi — a BMJ editor who has challenged other vaccine policies in the past — accuses WHO of breaching ethics guidelines by not getting parents’ written consent to take part in what he describes as research.

WHO disputes the claims, saying that the pilot is not experimental and that written consent is therefore not required. “The vaccine … [has] been authorized for use and is being rolled out in health clinics with other childhood immunizations,” Dr. Mary Hamel, lead for the RTS,S implementation program at WHO, told Devex. The BMJ article shows a “serious misunderstanding” about the pilot that could “have negative effects on the uptake of a vaccine that has the potential to save a lot of lives,” she said.

Malm agreed that the concerns are misplaced, saying: “The issue about consent is way off. It’s not a study anymore; it’s routine immunization … [and] we don’t get consent for routine immunization.” But the concerns have already been widely shared on social media.

Funding challenges

Even if the vaccine pilot goes well and WHO recommends a wider roll out, affordability could still be an issue.

While GSK has funded the work to date — reportedly sinking $1 billion into the project over the past 30 years and donating up to 10 million doses for the pilot — the company’s continued generosity is not guaranteed.

In principle, GSK has agreed to keep offering the vaccine at the price of production cost plus a 5% financial return, but this depends on there being enough demand for the vaccine and support from Gavi, the global vaccine alliance, a spokesperson for GSK told Devex by email.

GSK will “continue production at our manufacturing facility, provided an adequate funding mechanism is in place to finance the purchase of these doses,” the spokesperson wrote, adding that GSK is exploring options “to ensure longer-term cost-efficient vaccine manufacturing.”

Meanwhile, GSK CEO Emma Walmsley, who took over the role in 2017, has made it clear she wants the company to focus on more commercially viable research and has streamlined its Africa operations, raising concerns about GSK’s ongoing commitment to the project.

The company remains committed to serving patients in Africa, the spokesperson said.

Malm argued that “the biggest threat [to malaria efforts broadly] is withdrawal of funding.” While international and domestic support for Ghana’s malaria work has historically been steady, there is always the risk it could drop off due to complacency or pressure from competing priorities such as the COVID-19 pandemic, she said.

But stepping back from malaria now would be a disaster. “The thing about malaria is you can reduce it to a point, but if you don’t make sure it is stabilized, you get it back in even higher levels,” she said.

Whatever happens, Malm said she sees a role for the RTS,S vaccine, provided that the pilot shows positive results.

“The fight for malaria is so difficult — any intervention that will help us … is welcome,” she said.

Editor’s Note: The reporter’s travel to Ghana was supported by Malaria No More UK. Devex retains full editorial control of the content.