The R21 malaria vaccine was approved by the WHO in October 2023 and may well end up saving millions of lives. It is cheaper and easier to produce than the only other malaria vaccine, called RTS,S. 1Day Africa has launched a campaign to accelerate the deployment of R21. For every million children vaccinated, 1.9 million cases of malaria could be averted, and 6,000 children saved from death, according to one recent estimate.
But how did we get the R21 vaccine? As is very common for malaria vaccines, early research made use of human challenge trials. Volunteers were given the then-experimental vaccine and infected (“challenged”) with malaria to see if the vaccine might work (and volunteers are always eventually treated and cured, of course).
For R21, there were two human challenge trials, both held in the United Kingdom and run by the Jenner Institute at Oxford University. These two studies, called VAC 065 and VAC 072, helped zero in on the ideal formulation and schedule of the vaccine, which then moved on to the much more complicated, long-term field trials in Africa that generated the final data needed to confirm its safety and efficacy.
Paul Zimmer-Harwood, now a 1Day Sooner employee working on proposed hepatitis C human challenge trials, took part in one of the malaria challenge trials in 2018. We asked him about his experience:
Q: What was the structure of the study like? How did it affect your daily life?
After the screening phase, malaria was transmitted through mosquito bites in London because Imperial College London had the necessary facilities to handle the mosquitos — they needed several layers of barriers (i.e. walls/doors) between the mosquitos and the public. All of us in the study and some personnel took the train from Oxford.
The malaria parasite first invades the liver, where it replicates before it can be detected in the blood and before symptoms become noticeable. At this stage, the malaria is not infectious. Given that the focus of the study was on the success or failure of the progression of the initial infection, it necessitated daily hospital visits, both in the morning and evening, for approximately ten days. I was pretty flexible as a PhD student, so it was not too big of a deal (and I was even able to participate in a rowing competition during it, thankfully).
The purpose of the appointments was to detect the presence of merozoites, the form of the malaria parasite that invades red blood cells, as early as possible in our blood once the infection had moved beyond the liver stage and to be able to swiftly initiate treatment.
Q: What was the challenge like? Did you feel any symptoms of malaria?
In the vaccine study, a select group of participants, including myself, were intentionally infected with malaria without prior vaccination as a control. The rationale for this approach was to verify the effectiveness of the infection method, ensuring that any observed vaccine efficacy wasn’t merely a result of a faulty infection technique. Being part of this group, I was aware from the outset that I was likely to contract full malaria and develop symptoms.
Probably around 10 or 11 days after we were challenged did it appear for me. I didn’t even realize it until I had gotten the call from them after I had done that day’s blood testing in the morning. I started feeling sick that night. The fever classically comes in waves, and it was pretty awful — I woke up in a sweat at night and had some weird dreams. I also felt really weak during these waves.
What’s interesting about malaria is that when these waves subside, you feel relatively normal — I was able to show some friends visiting from Germany around during the next day and went to work, and then it came back again that night. By the third day I was mostly recovered with the treatment provided.
Q: What was it like walking around after you were challenged knowing you had malaria sporozoites hanging out in your liver?
Honestly, it didn’t occupy my thoughts excessively. It’s worth acknowledging that our bodies inherently house roughly as many bacterial cells as human cells, albeit bacterial cells are significantly smaller on average. In addition to bacteria, we also host fungi, archaea, and other microorganisms. As a fun point of reference, I suggest a quick web-search on “face mites” which most humans carry. Even prior to the study, I was a living biotope.
Q: Did you hear more from the study team after your study ended?
No. Most medical studies don’t tell participants about the results, which is unfortunate.
Q: What motivated you to join the study?
When I was an undergrad at Oxford in cognitive science, I joined various studies — like questionnaires — to help friends doing research. One funny one involved me sitting blindfolded in a chair that rotated around, and I had to guess which rotation was larger. Way harder than malaria or COVID-19 was a study about metabolism that was also at Oxford. It was about the effect of ketones (the drink they had me consume at the time cost about £1 per milliliter!), and I had to bike for two hours at 70% of my max heart rate, and then do a ramp test until exhaustion. All before breakfast. I was so exhausted at the end of each test that I had to take a nap before I could get anything else done after each morning.
When I learned about the malaria study, I was already well accustomed to participating in research. The study seemed more impactful — and the money was a motivator, too. In that sense it wasn’t too hard to decide to join.