Researchers have bred a hybrid malaria parasite that invades human cells far more efficiently than the strain now being tested in next generation malaria vaccines. Although creating a more capable parasite may sound alarming, the work could support efforts to develop stronger protection against the deadly disease.

The hybrid could provide a parasite better suited for harvesting and capable of stimulating a powerful immune response. Researchers hope the approach could eventually contribute to a single dose vaccine that works across a wide population.

The existing RTS,S vaccine has demonstrated benefits, but its protection remains limited. A randomized rollout across Ghana, Kenya, and Malawi reduced deaths while preventing only around 39% of malaria cases after four doses.

One reason for that limitation is the vaccine’s composition. RTS,S contains only a single protein from Plasmodium falciparum, the parasite responsible for malaria, rather than using the entire organism to provoke an immune response.

An alternative strategy uses a genetically weakened version of the whole parasite. Small trials in their early phases have suggested that this approach could be highly effective, including one striking result reported in 2025.

In that trial, a single dose protected nine of the 10 people who received it. The outcome raised hopes that strong protection might not require several separate doses.

“This remarkable and unprecedented result suggests that a single-dose vaccine for malaria might be an achievable goal,” wrote Stefan Kappe and Debashree Goswami in a commentary accompanying the trial. Kappe is an inventor of PfSPZ-LARC2, one of the whole parasite vaccine candidates currently undergoing clinical trials.

The parasites used for such vaccines are genetically engineered to die inside the liver. That prevents them from reaching the bloodstream, a step they must complete to cause malaria.

Producing the vaccine presents another challenge because scientists first need to harvest enough parasites. The process is currently viable only with a malaria strain called NF54, first collected in 1979, that can yield more than 100,000 parasites from each insect.

NF54 has two significant limitations. It enters the liver relatively poorly, restricting how much the immune system can benefit, and it more closely reflects Plasmodium falciparum strains from 1979 than present day strains.

Researchers developed a hybrid called AV27 in an effort to address both shortcomings. They allowed two different malaria parasite strains to breed inside a mosquito and then selected offspring displaying the most promising characteristics.

Half of AV27’s genome comes from NF54. The other half comes from MAL31, a parasite collected in Malawi in 2016, giving the hybrid genetic material from both an established vaccine production strain and a more recently collected parasite.

The team tested AV27 in mice whose livers had been rebuilt with human cells, making them more useful models of human health. AV27 entered the liver roughly 15 times more efficiently than NF54 while still producing approximately the same number of parasites per insect.

AV27 also inherited about 90% of the immune targets found in each parent. That combination could allow researchers to produce large parasite quantities while exposing the immune system to a broad collection of targets.

“A parasite that develops in the liver 15 times more efficiently should be able to do more with a smaller dose,” said study author Ashley M. Vaughan at the Seattle Children's Research Institute in a statement. “Whether that translates into greater protection in people is the question a clinical trial has to answer.”

AV27 is not itself a vaccine because researchers have not genetically weakened it. A version prepared for vaccine use would carry the same two gene deletions as PfSPZ-LARC2, which is being tested in Burkina Faso, Mali, the US, and Germany.

Those trials are expected to report their first efficacy results in early 2027. They must also establish whether the vaccines protect against parasites that are genetically distant from the strain used to create them, something no trial has yet demonstrated.

The researchers stressed that AV27 is no more dangerous than existing strains. It is not more virulent, transmissible, or drug resistant, and every genetic sequence it contains already circulates among parasites in Africa.

The same kind of genetic reshuffling occurs naturally when two malaria strains meet inside a mosquito. For now, AV27 offers researchers a potential route toward producing a weakened whole parasite vaccine that combines strong liver invasion with high yields from each insect.