Scientists breed a 'pan-African' malaria parasite to build a better whole-parasite malaria vaccine

ROCKVILLE, Maryland / SEATTLE, Washington / /  November 11, 2026 — Researchers have created a hybrid malaria parasite that combines the manufacturing advantages of the strain used in every current whole-parasite malaria vaccine with the much higher liver infectivity of a parasite collected recently in East Africa. The work is published in JCI Insight.

The hybrid, called AV27, was made by letting two Plasmodium falciparum parasite strains mate inside mosquitoes — the parasite's own natural sexual cycle — and then selecting the offspring with the most useful combination of inherited traits. No genes were added, removed or redesigned to make AV27. Every gene it carries already circulates in parasites in Africa today.

AV27 is the intended parasite to be used for a next-generation version of Sanaria's PfSPZ-LARC2 Vaccine. Like the current vaccine, that candidate will be fully attenuated: two of its genes are deleted so the parasite matures inside liver cells and then dies there, without ever entering the bloodstream, where malaria illness begins.

The problem: one 1979 parasite underpins every PfSPZ vaccine

Malaria caused more clinical cases and more deaths in 2024 than in 2015, despite more than $4.5 billion spent annually on control. A highly effective vaccine is still missing.

PfSPZ vaccines take a different approach from vaccines built around one or two parasite proteins. They use the whole parasite at its sporozoite stage — the form a mosquito injects — so the immune system sees thousands of parasite antigens at once. These vaccines have produced 100% protection against controlled infection in clinical trials, and, in a Phase 2 trial published earlier this year, roughly 50–56% protection in malaria-naïve Indonesian soldiers deployed to Papua.

Every PfSPZ vaccine made so far rests on a single parasite strain, NF54, isolated near a Dutch airport in 1979 from a West African source. NF54 was chosen for one practical reason: it produces enormous numbers of sporozoites in mosquitoes — more than 100,000 per insect — which is what makes manufacturing possible at all. But NF54 has two limits. It is comparatively poor at invading human liver cells, up to eight times worse than parasites collected more recently. And its repertoire of immune targets reflects West Africa in 1979, not the parasites circulating across the continent now.

What the team did: selective breeding, not engineering

Malaria parasites reproduce sexually, and they do it inside the mosquito. When a mosquito takes blood from a person carrying two different parasite strains — an everyday event in high-transmission areas — the two strains mate and their offspring carry a shuffled mixture of both genomes.

The researchers reproduced that process deliberately. They fed mosquitoes a blood meal containing the sexual stages of NF54 together with one of three recently collected East African parasites: MAL31 and NF165 from Malawi, and HL1209 from a traveller to South Sudan. The resulting sporozoites were used to infect mice with humanized livers, which allowed the hybrid offspring to be recovered and grown as single clones.

From three crosses the team screened 117 clones, identified 82 hybrids, sequenced the genomes of 62 of them, and then tested the most promising eight for the traits a vaccine strain actually needs. This is selective breeding, the same logic used for centuries in agriculture, applied to a parasite and read out with modern genomics.

What they found

One clone, AV27 — the offspring of NF54 and the Malawian isolate MAL31 — inherited the best of both parents.

Roughly half its genome came from each parent. A complete, gapped-free genome assembly showed about 50% NF54 and about 50% MAL31 across the chromosomes.

It reaches the human liver about 15 times more efficiently than NF54. In mice whose livers had been repopulated with human liver cells, AV27 and NF54 sporozoites were injected together into the same animal. Six days later, 94% of the liver-stage parasites were AV27 and 6% were NF54. AV27 also formed noticeably larger liver-stage parasites, a feature associated in earlier work with stronger T cell responses.

It can still be manufactured. Across eleven production runs between 2023 and 2025, AV27 yielded a median of 78,179 sporozoites per mosquito, statistically indistinguishable from NF54's median of 62,388 across twelve runs in the same facility. The East African parent MAL31, by contrast, managed a median of 3,134 — far too few for cost-effective vaccine production. That combination, high yield plus high liver infectivity, is what neither parent could offer alone.

It carries immune targets from both East and West Africa. PfSPZ vaccines are thought to work mainly through CD8+ T cells that recognize short parasite peptides displayed on infected liver cells. Predicting those peptides across 26 common human HLA types, the team found that AV27 retains about 90% of the predicted repertoire of each parent: 80.2% of its peptides are shared by both, 9.5% come only from West African NF54, and 10.3% only from East African MAL31.

The traits held up over time. AV27's sporozoite output and liver infectivity stayed consistent across independent production lots made months apart, after 11 and 14 rounds of culture passage.

What this work is, and what it is not

Because whole-organism vaccines are unfamiliar to many readers, the authors are explicit about the nature of this research.

This is a parasite, not a virus. Plasmodium falciparum is a single-celled eukaryote with a 23-million-base-pair genome and roughly 5,300 genes. It cannot spread from person to person. It requires a female Anopheles mosquito to complete its life cycle, and in the laboratory it is grown only in purpose-built, aseptic, triple-screened insectaries.

This is not gain-of-function research. No genetic material was introduced, deleted or synthesized to create AV27. The parasites were allowed to mate, and the researchers selected among naturally arising offspring. Every sequence in AV27 is already present in parasites circulating in Africa. The same recombination happens continuously in the field wherever two strains infect one mosquito.

AV27 is not more dangerous than the parasites it came from. It is no more virulent, no more transmissible and no more drug resistant than either parent. Its higher liver infectivity is inherited from a recently collected field isolate, and it is well within the range seen in natural isolates — the South Sudanese isolate HL1209 was about 30 times more liver-infective than NF54, twice AV27's figure. In other words, AV27 does not exceed what parasites already do in nature. What is new is the combination of that ordinary field trait with the manufacturability of NF54.

The vaccine will be fully attenuated and cannot cause malaria. AV27 will not be used as a vaccine in the form described in this paper. As with the current PfSPZ-LARC2 candidate, two genes (PfMei2 and PfLINUP) will be deleted. The parasite then completes liver-stage development, presenting a full load of antigen to the immune system, but cannot produce the merozoites needed to enter red blood cells. It dies in the liver. It cannot cause malaria illness, and it cannot be picked up by a mosquito and passed on.

No humans were involved in this study. The work used laboratory cell culture,  mosquitoes and mice with humanized livers, and was reviewed and approved by the Seattle Children's Research Institute Institutional Animal Care and Use Committee.

"We did not engineer this parasite. We let two parasites mate, the way they do every day inside mosquitoes in Africa, and then we chose the offspring that inherited the traits a vaccine needs," said Dr. B. Kim Lee Sim, senior author and Executive Vice President of Process Development and Manufacturing at Sanaria Inc. "What makes AV27 unusual is that it is good at two things at once. Until now we had to choose between a strain we could manufacture and a strain that infects the liver well."

"A parasite that develops in the liver 15 times more efficiently should be able to do more with a smaller dose," said Dr. Ashley M. Vaughan, Center for Global Infectious Disease Research, Seattle Children's Research Institute. "That matters for cost, and cost matters a great deal for a vaccine intended for sub-Saharan Africa. Whether it translates into greater protection in people is the question a clinical trial has to answer."

"Immunity from these vaccines depends on T cells recognizing parasite peptides on infected liver cells, so the vaccine's peptide repertoire matters, said Dr. Stefan Kappe, an inventor of PfSPZ-LARC2 Vaccine, who is the Director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. "AV27 retains about 90% of the predicted repertoire of each parent. It is the first vaccine substrate that represents both East and West African parasites in one organism."

"Every whole-parasite malaria vaccine in the world today descends from a parasite isolated in 1979," said Dr. Stephen L. Hoffman, CEO of Sanaria Inc. "This is the first serious attempt to replace that foundation, and it establishes a method we can use again — for Southeast Asia, for Oceania, for South America."

What comes next

The current lead candidate, PfSPZ-LARC2 Vaccine, is built on NF54 and carries the two attenuating gene deletions. It has been shown to be fully attenuated, safe and immunogenic, and is in Phase 1 trials in Burkina Faso, the United States and Germany, and Phase 2 trials in Burkina Faso and Mali. Protective efficacy results are expected in the first quarter of 2027.

The AV27-based candidate, provisionally PfSPZ-LARC2 (AV27), will carry the same deletions. The authors' expectation is that its higher liver infectivity will allow equivalent immune responses at a lower dose, and that its broader peptide repertoire will widen protection across Africa. Both expectations are hypotheses that clinical trials will have to test.

The method itself may prove as important as the strain. The same approach could be used to breed vaccine substrates matched to the parasites of Southeast Asia, Oceania and South America.

What the study does not show

The authors are direct about the limits of the work. Liver infectivity in humanized mice and predicted T cell peptides are surrogates for vaccine potency, not measurements of it. No efficacy claim can be made until an AV27-based vaccine is tested in people. The team also notes that it assessed a relatively small number of crosses and hybrid clones, which may not capture the full range of possible outcomes, and that the biological reasons for NF54's unusually high sporozoite production and for field isolates' high liver infectivity remain unknown.

Collaborators, funding and data

The study was a collaboration between the Center for Global Infectious Disease Research at Seattle Children's Research Institute; Sanaria Inc., Rockville, Maryland; the Institute for Genome Sciences, University of Maryland School of Medicine; The Pennsylvania State University; the Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa; and the University of Washington.

Funding came from the US National Institutes of Health: grant U01 AI155356 to B. Kim Lee Sim and grant P01 AI127388 to Ashley M. Vaughan.

All whole-genome sequencing data are publicly available from NCBI's Sequence Read Archive under BioProject PRJNA1235678. The parasite strains will be made available to the research community on reasonable request under material transfer agreements.

Competing interests: several authors are employees of Sanaria Inc.; B. Kim Lee Sim and Stephen L. Hoffman own stock in Sanaria.

Publication: Pazzagli L, Jenkins B, Dwivedi A, et al. Pan-African hybridization of PfSPZ increases antigenic diversity and replicative capacity for malaria vaccine design. JCI Insight. 2026;11(18):e207272. DOI: 10.1172/jci.insight.207272

Publication Link: https://insight.jci.org/articles/view/207272

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About Sanaria Inc.

Founded in 2003, Sanaria is committed to developing groundbreaking malaria vaccines, offering sustained protection against Plasmodium falciparum. Headquartered in Rockville, Maryland, we are a leader in malaria vaccine innovation. Our name—drawn from the Italian mal’aria (“bad air”)—symbolizes our mission to bring a breath of healthy air to the fight against malaria, with vaccines designed not only to prevent disease, but also to interrupt transmission and enable targeted elimination. With over $430M invested to date, Sanaria has secured 79 worldwide patents with 14 applications pending.  The company is actively seeking partners to further advance its vaccine technologies. Learn more at https://sanaria.com/.

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