In a discussion with Malaria No More, Dr. Stephen Hoffman, CEO of biotechnology company Sanaria, discusses his company’s latest progress toward a single-dose malaria vaccine with the development of Sanaria®PfSPZ-LARC2 Vaccine, developed in collaboration with the Kappe lab at Seattle Children’s Research Institute (SCRI).
You describe the PfSPZ-LARC2 malaria vaccine as groundbreaking. Why?
HOFFMAN: Sanaria’s PfSPZ vaccines are the only malaria vaccines that have ever achieved 90% protection against controlled human malaria infection (CHMI) with any dosage regimen, a milestone now achieved by two different PfSPZ vaccines. What makes this vaccine, its most advanced vaccine candidate, so potentially groundbreaking, is that recent data from a clinical trial in the Netherlands with a similar approach achieved an unprecedented 90% protection against CHMI with a single-dose. Thus, we see the introduction of PfSPZ-LARC2 Vaccine as a potentially game-changing development that could prevent the death of hundreds of thousands of children and help eliminate malaria using the simplest possible vaccination regimen.
Getting to this point hasn’t been easy. Developing a highly protective, cost-effective malaria vaccine is something we’ve been working on for nearly two decades. Together with researchers at Seattle Children’s Research Institute’s Center for Global Infectious Disease Research (CGIDR), we used genetic engineering to develop PfSPZ-LARC2 Vaccine, which is uniquely able to replicate (multiply) in the liver without developing to the parasite stages that causes malaria symptoms and pathology and transmit malaria parasites to mosquitoes. The replication of parasites in the liver stimulates a very strong immune response against the Plasmodium falciparium (Pf) parasite, the parasite that causes more than 95% of deaths from malaria. As you know, Pf grows in mosquitoes and is transmitted by bite to humans, where it infects the liver, replicates, merges into the bloodstream and infects red blood cells, causing disease and sometimes death. But PfSPZ-LARC2 Vaccine disintegrates in the liver after completing replication, preventing new parasites from getting into the bloodstream.
Right now, the only approved malaria vaccines are the RTS,S and R21 vaccines. Both vaccines target only one of the more than 5,000 Pf parasite proteins. This type of approach offers moderate protection against malaria disease in children. However, because of their modest efficacy, and because they have not been shown to prevent Pf infections, most malariologists do not consider these single antigen vaccines adequate to eliminate malaria. If the parasite develops to the blood stage, it can be transmitted to the mosquitoes that spread the malaria parasite.
With PfSPZ-LARC2 Vaccine, we use the live attenuated (weakened) whole parasite with all of its 5,000 genes , so we’re able to target a broad range of antigens. This not only prevents symptoms of malaria but also blocks infection, which ultimately helps stop transmission.
We’re very excited about this, because our latest research shows that the high level of protection seen with PfSPZ vaccines evaluated by CHMI in early phase studies translate to significant protection against naturally transmitted Pf in Phase 2 trials conducted in the field, inducing immunity that protects against Pf infection for two years without boosting, including in pregnancy.
Why have you been focusing on developing a single-shot malaria vaccine?
HOFFMAN: A single-shot malaria vaccine has the potential to significantly simplify the vaccination process and lead to many more people being protected. Current multi-dose regimens require multiple visits, which can be challenging for families, especially with young children. A single-dose vaccine reduces the logistical challenges, lowers costs, and ensures more children receive full protection. This would be an unprecedented breakthrough toward accelerating Pf malaria elimination by providing a more efficient tool to prevent infections and reduce transmission.
What needs to happen next?
HOFFMAN: PfSPZ-LARC2 has two genes deleted, mei2 and LINUP; the “2” stands for the 2 deleted genes. Researchers at Leiden University Medical Center produced a parasite that has one of these two genes deleted, the mei2 gene. They call the parasite GA2 and Sanaria and SCRI call it PfSPZ-LARC1. In a clinical trial in Leiden they assessed single immunization by mosquito bite with GA2 (aka PfSPZ-LARC1) and showed that it provided 90% protection against CHMI. This pivotal result was published in the prestigious journal, Nature Medicine, in January 2025, showcasing the remarkable potential of LARC vaccines.
But GA2 was administered by mosquito bites, which we can’t use for deploying vaccines. In contrast PfSPZ-LARC2 Vaccine has been manufactured as an injectable vaccine that meets regulatory standards for clinical development and can be manufactured and distributed on a large scale.
This year, PfSPZ-LARC2 Vaccine trials are scheduled to take place in the U.S., Germany, and Burkina Faso. Researchers will be evaluating the vaccine’s safety and efficacy in diverse populations and environments. Within the next three years, we expect the results from these trials to provide critical insights into the vaccine’s global deployment potential.
But already, the LARC single-dose regimen is garnering enthusiastic support from leading experts for unparalleled protection rates, and potential for broad accessibility, so we are thrilled that by targeting the parasite at a critical stage in its life cycle, this vaccine could finally make malaria elimination a reality.
The introduction of PfSPZ-LARC2 Vaccine to prevent infection, clinical disease, and transmission is timely as it comes at a time of increasing Pf drug resistance, the spread of malaria due to climate change, and uncertainty of government commitments to global health, all which have the potential to lead to rapid increases in malaria cases and deaths.
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