Experimental two‑in‑one vaccine shows success in human LASSARAB trial

Researchers from Thomas Jefferson University and the University of Maryland School of Medicine have reported encouraging results from the first human clinical trial of LASSARAB, an experimental vaccine designed to protect against Lassa fever and rabies in a single formulation. The findings, published in the journal Nature Medicine, show that the vaccine was well tolerated and induced robust immune responses against both viruses in healthy adult volunteers.

Lassa fever, which is caused by the virus, is a severe hemorrhagic disease that is endemic to parts of West Africa, causing an estimated 300,000 to 500,000 infections and over 5,000 deaths each year. The disease can lead to severe complications, including organ failure, hearing loss and long-term neurological disorders. Currently, there are no licensed vaccines to prevent Lassa fever, but the LASSARAB platform may offer a practical and scalable solution for endemic regions with limited resources.

LASSARAB is based on an inactivated rabies virus vector, which is engineered to express the Lassa virus glycoprotein complex (GPC) and with a synthetic adjuvant, which enhances immune response. LASSARAB leverages the rabies vaccine's long-established safety record, enduring immunity, existing manufacturing infrastructure and global distribution networks. Among the three Lassa fever vaccines currently under development, LASSARAB is the only candidate based on a killed or attenuated virus.

In this randomized Phase 1 trial, featured as one of Nature Medicine's "Eleven clinical trials that will shape medicine in 2026," 54 male and female adults aged 18 through 50 years old were split into four groups. They either received two intramuscular doses of LASSARAB at increasing (low, medium and high) dose levels or a licensed rabies vaccine as a control. Across all vaccine dose groups, no serious adverse events or severe reactions were observed and reported side effects (such as injection‑site tenderness, pain and mild flu‑like symptoms) were temporary and resolved without additional treatment. 

Importantly, the vaccine demonstrated a strong immune response. By 61 days after the first dose, 100% of LASSARAB recipients developed Lassa virus–specific antibodies, while all control participants did not. At the same time, all participants receiving LASSARAB achieved levels of neutralizing antibody against the rabies virus that exceed the World Health Organization's established threshold for protection, matching responses seen with licensed rabies vaccines.

"These results provide the first clinical evidence that a rabies‑vectored platform can safely generate immunity to Lassa virus in humans," says senior author Matthias J. Schnell, PhD, director of the Jefferson Center for Vaccines and Pandemic Preparedness and chair of the department of microbiology and immunology at the Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Schnell has played a pivotal role in establishing rabies virus (RABV)–based vectors as a versatile platform for vaccines against high-consequence infectious diseases. "The ability to combine protection against Lassa fever and rabies in a single vaccine could have a substantial public‑health impact in regions where both diseases remain endemic."

In this first-in-human study, the LASSARAB vaccine showed promising early results, with the potential to provide dual protection against both diseases in a single product. If confirmed in further studies, this approach could represent a meaningful advance for global health."

Justin Ortiz, MD, MS, Center for Vaccine Development and Global Health and principal investigator on the clinical trial

The investigators emphasize that this was an early‑stage trial designed to assess safety and immune responses, not efficacy. Longer‑term follow‑up and larger studies in populations where Lassa fever is endemic will be needed to determine the durability of protection and real‑world effectiveness. Nonetheless, the results support continued clinical development of LASSARAB as a next‑generation, dual‑purpose vaccine targeting two major global health threats.