Groundbreaking malaria vaccine provides high-level protection with just one dose

Scientists at Sanaria and Seattle Children's Research Institute's Center for Global Infectious Disease Research (CGIDR) have unveiled a groundbreaking malaria vaccine, Sanaria^® PfSPZ-LARC2 Vaccine, designed to provide high-level protection with just one dose. This innovative approach leverages decades of research and cutting-edge genetic engineering to combat one of the world's deadliest diseases.

Malaria continues to impose a devastating burden worldwide, with 263 million cases and nearly 600,000 deaths reported in 2023, most of those being in children under 5. The World Health Organization (WHO) has called for an ambitious goal of 90% protection against Plasmodium falciparum (Pf) infection. Despite significant investment and the introduction of vaccines such as RTS,S and R21, that goal has not been attained. Recent data suggest that PfSPZ-LARC2's single-dose approach could redefine malaria prevention and elimination efforts globally and have put the WHO goal within sight.

The science behind the PfSPZ-LARC2 vaccine

LARC (Late liver stage-Arresting and Replication-Competent) describes genetically weakened parasites that replicate in the liver, but halt progression before reaching the blood stage, ensuring the recipient of the vaccine remains safe, symptom-free from malaria, and protected from disease. Using advanced genetic engineering, researchers deleted two critical parasite genes, Mei2 and LINUP, from the Pf genome. These deletions ensure that the parasites replicate in the liver but cannot advance to the blood stage, rendering the vaccine incapable of causing disease or transmitting, while preserving protection.

This innovative dual-gene deletion approach builds on the team's earlier research with PfSPZ-LARC1, in which only the Mei2 gene was deleted. By adding the LINUP deletion, the team further increased the vaccine's safety, making LARC2 a promising candidate for widespread use. Preclinical studies have shown that LARC vaccines are significantly more potent and protective than existing options.

Promising results and future trials

A pivotal study published in Nature Medicine in January 2025 showcased the remarkable potential of LARC vaccines. Researchers at Leiden University Medical Center tested a LARC1 parasite with the deletion of the Mei2 gene alone (called GA2 by the Leiden team) and demonstrated that this provided 90% protection against controlled human malaria infection (CHMI) after a single immunization via mosquito bite-an unprecedented result in malaria vaccine research.

The success of GA2 strongly validates the use of genetically weakened parasites to achieve high levels of immunity. While GA2 demonstrated exceptional efficacy with a single-gene deletion (Mei2), the PfSPZ-LARC2 Vaccine builds upon this foundation by incorporating dual deletions to ensure that PfSPZ-LARC2 preserves the protective efficacy observed in GA2 while meeting rigorous safety standards necessary for widespread use.

Although GA2 demonstrated exceptional efficacy, its administration method (via mosquito bites) cannot be used for a deployed vaccine. In contrast, the injectable PfSPZ-LARC2 Vaccine meets regulatory standards for clinical development and can be manufactured and distributed on a large scale.

Clinical trials of PfSPZ-LARC2 are scheduled for 2025 in the U.S., Germany, and Burkina Faso. These trials will evaluate the vaccine's safety and efficacy in diverse populations and environments. Results from these trials are expected to provide critical insights into the vaccine's global deployment potential within the next three years.

Expert commentary

The breakthrough has garnered enthusiastic support from leading experts:

"We are excited about assessing PfSPZ-LARC2 Vaccine in Burkina Faso, as it is the only malaria vaccine in development that has the potential of achieving the WHO goal of at least 90% protection against Pf infection," said Professor Sodiomon Sirima of GRAS (Groupe de Recherche Action en Santé) and principal investigator on the upcoming Burkina Faso trial.

We have worked for two decades to develop a highly protective, cost-effective PfSPZ vaccine. PfSPZ vaccines have provided the highest levels of protection against controlled human malaria infection and the only malaria vaccines shown to protect against Pf infection for two years without boosting, including in pregnancy. PfSPZ-LARC2 Vaccine is our 3rd generation vaccine, and expected to be our flagship going forward."

Dr. Stephen L. Hoffman, Sanaria's CEO

In a News & Views article in Nature Medicine, Dr. Stefan Kappe of CGIDR pointed out that immunization with GA2 gave unprecedented protection against malaria infection with a single shot, indicating that LARC vaccines are potentially transformational tools that could make malaria eradication with a vaccine a reality.

Addressing the global malaria crisis

Despite over $4 billion in annual investments for malaria control measures, global case numbers and deaths have remained stagnant over the past decade. The WHO's call for a vaccine that provides at least 90% protection underscores the urgent need for innovative solutions. The development of PfSPZ-LARC2 Vaccine to prevent infection, clinical disease, and transmission is timely as it comes at a time of increasing Pf drug resistance, enhancing 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.

PfSPZ-LARC2 Vaccine's single-dose regimen, unparalleled protection rates, and potential for broad accessibility position it as a game-changer in global health efforts. By targeting the parasite at a critical stage of its life cycle, this vaccine could finally make malaria elimination a reality.