An experimental vaccine that targets a malaria parasite behind a relapsing form of the disease has shown some promise in a small trial. Researchers tested two vaccine candidates, finding that neither had any serious safety concerns, but only one induced a substantial immune response.
The parasite Plasmodium vivax is the second most common cause of malaria in the world, responsible for 4.9 million cases in 2021. Unlike Plasmodium falciparum, the parasite that most commonly causes malaria, no vaccine is approved for P. vivax, which can remain dormant in the body and cause a relapse of symptoms.
Mimi Hou at the University of Oxford and her colleagues have developed two vaccines against P. vivax, which both target the so-called Plasmodium vivax Duffy binding protein. Previous studies have found that people who lack a receptor for this protein in their red blood cells appear to be more resistant to P. vivax.
One of the vaccines, a viral vector vaccine, uses a modified virus to deliver the parasite’s genetic information to cells to induce an immune response. The other, a protein-based vaccine, does this by introducing some of the parasite’s proteins.
In a trial of 18 healthy volunteers – aged 18 to 45 – eight received the viral vector vaccine, while the other 10 received the protein-based vaccine. Due to the covid-19 pandemic disrupting the trial, the timing of different vaccine doses varied among the participants.
Between two and four weeks after their final vaccine dose, the participants were injected with blood containing P. vivax. The team also injected 13 people who weren’t given either vaccine to act as the control group.
Both types of vaccine were well tolerated and no serious adverse effects were reported.
When it came to the immune response, this was much stronger in those who received the protein-based vaccine, but only in those with a long gap between their second and third doses. Of the 10 protein-vaccine recipients, six received their third dose 13 months after their second dose, compared with a one-month gap for the remaining four participants.
The parasite’s multiplication rate was 51 per cent lower in these six participants than in the control group. This led to these vaccine recipients developing malaria symptoms around a week after everyone else. However, the symptoms weren’t less severe, says Hou. Among the four participants with a one-month dosing interval, the team found no difference in their parasites’ multiplication rate compared with the unvaccinated controls.
Protein-based vaccines generally stimulate antibody responses more effectively than vector-based ones, says Hou. Meanwhile, the increased success rate of the protein-containing vaccine when given with a delayed dosing interval has been seen in other vaccines, she says. “We don’t understand how it works in detail, but it’s probably related to giving the immune system more time to develop a good response.”
The researchers are now testing the vaccine in a larger trial. They also plan to use the study’s results to create a new vaccine that is even more effective at preventing the parasite from replicating in the blood. “I think one of the really happy things about seeing these results is that we can actually induce an effect,” says Hou. “It might not be strong enough yet, but we know that it’s possible.”
Science Translational Medicine DOI: 10.1126/scitranslmed.adf1782