For the first time, the world is starting to roll out malaria vaccines to children in sub-Saharan Africa. The story of the development of those vaccines, a decades-long effort that stretched from labs in New York, England, and Belgium to clinical research sites in a number of African countries, is detailed in a STAT special report published Thursday.
Below are four takeaways about what the history of the malaria shots shows about vaccine development, particularly for neglected diseases that primarily affect low-income countries.
Science builds
Sometimes scientific discoveries are attributed to individual champions. But if you talk with researchers, they stress that really, science snowballs, with initial findings enabling future breakthroughs. That was clear in the case of the malaria vaccines.
The architects of the shots, for example, relied on foundational work done by researchers like New York University’s Ruth and Victor Nussenzweig, a couple who met while in medical school in Brazil. Joe Cohen, who helped lead the development of the RTS,S malaria vaccine at GSK, leveraged the company’s prior work on a hepatitis B vaccine. When University of Oxford researchers built their own malaria vaccine, called R21, two decades later, they were taking advantage of advances in basic research tools that had emerged in the interim.
The vaccines underscore how scientific success often rests on people chipping away at knotty problems over years — particularly when the target is as complex as a parasite like the one that causes malaria — and not a single discovery made in isolation.
Commercial prospects influence vaccine development
It’s well established that pharma companies aren’t always interested in developing medicines or vaccines for diseases if they can’t make a good return off of them, including many afflictions of the world’s poorest countries. That dynamic — on top of the scientific challenge inherent in trying to prevent malaria — helps explain why it took so long for the shots to arrive.
In the case of RTS,S, GSK was deeply involved in inventing, advancing, and manufacturing the vaccine over decades. But there was also a whole lot of work and money put in by other groups to prop up the vaccine at particularly precarious moments — and to incentivize GSK to keep the program alive. If there had been a promise of profits, the process may have been smoother.
Experts involved in the development of the vaccines also pointed to another financial factor that slowed them down. With potentially lucrative products at stake, companies will do everything they can to expedite development, including organizing future trials and scaling up manufacturing while earlier study is still underway. But with RTS,S, the research teams couldn’t really start planning and fundraising for their next study until the earlier one was fully wrapped up and had demonstrated success; otherwise, they would not have been able to get donors on board. It explains why there were often long gaps between the key studies of RTS,S.
A possible alternative path
If it’s going to be difficult to get pharma on board to develop more vaccines and treatments for neglected diseases, what can be done?
The experience with R21 points to another pathway, said Adrian Hill, the director of Oxford’s Jenner Institute and one of the developers of the vaccine. The Oxford team partnered directly with the Serum Institute of India, the world’s largest vaccine manufacturer, which went on to fund R21’s Phase 3 trial.
Hill is now encouraging other academic teams working on neglected diseases to consider teaming directly with large manufacturers. That way, the researchers won’t have to entice a biopharma company to agree to become a development partner. The economics of vaccine development for diseases of the world’s poorest countries don’t align with the business models of those companies, Hill said. They want to sell a vaccine dose for a few hundred dollars, but the international agencies that buy vaccines for low-income countries can only afford a few dollars a dose.
Manufacturers have a different model.
“This is what I preach about at the moment,” Hill said about working with manufacturers. “They will look at manufacturability, they’ll look at cost of manufacture. If they figure out they can make it for $1, and they can sell it for $2, they’re happy.”
The Covid question
The world rallied to develop Covid-19 vaccines in record time. Many African researchers who spoke with STAT pointed to that feat to make the case that scientists, companies, and regulators know how to speed the development of vaccines when they want to. So where has that urgency been with malaria?
To be clear, there are key differences between malaria and Covid that influenced how quickly their respective vaccines were developed. For one, the coronavirus that causes Covid is a much simpler target to build a vaccine against. Another distinction: Unlike with Covid, the primary population being targeted for malaria shots is babies. But researchers first had to demonstrate the safety of the vaccines in older populations before they could ethically test the shots in youngsters, which added years to development timelines. There are also other interventions — including bed nets and chemoprevention — that can help reduce the risk of malaria. The world didn’t have many defenses when Covid struck.
Still, the effort to develop malaria vaccines saw nowhere near the kind of public health campaign or money that greeted the Covid pandemic. Many experts — in Africa, Europe, and the U.S. — cite the fact that the disease almost entirely affects people living in poor countries as part of the reason the world hasn’t moved with such haste.
“If you can see the speed that Covid had, from the alarm and then to get the vaccine — it was less than one year,” said Eusebio Macete, a Mozambican researcher. “So people ask, what’s wrong with the communicable diseases in Africa? Why should we spend years and years of people dying, without those tools?”
