For decades, Lassa fever has killed thousands of people across West Africa every year with no vaccine available to stop it. Now, an early-stage human trial suggests a novel two-in-one vaccine candidate — one that also targets rabies — may finally change that.
Researchers at the University of Maryland School of Medicine’s (UMSOM) Center for Vaccine Development and Global Health, in collaboration with Thomas Jefferson University, reported results June 18 from a first-in-human clinical trial of an investigational vaccine called LASSARAB. The findings, published in Nature Medicine, showed the vaccine was safe and generated strong immune responses against both Lassa virus and rabies virus in healthy adult volunteers — a notable milestone given that no licensed vaccine against Lassa fever currently exists anywhere in the world.
A dual threat in the same regions
Lassa fever is a viral hemorrhagic disease endemic to West Africa, transmitted primarily through contact with rodent urine or feces, with additional risk from person-to-person spread via bodily fluids. According to the Africa Centers for Disease Control and Prevention, the virus infects roughly 300,000 people and kills about 5,000 annually, though limited surveillance in affected countries means the true toll is likely higher. The disease is especially dangerous during pregnancy, where more than 80% of late-term infections end in the death of the mother, the fetus, or both. The World Health Organization has designated Lassa virus a priority pathogen for research and development.
Rabies, meanwhile, is almost universally fatal once symptoms appear and continues to kill thousands of people each year in many of the same West African and sub-Saharan communities where Lassa virus circulates. Combining protection against both diseases into a single product, researchers say, could simplify vaccination logistics in places where health infrastructure and delivery systems are already stretched thin.
How the vaccine works, and what the trial found
LASSARAB was developed by a research team at Thomas Jefferson University. It consists of an inactivated (killed) rabies virus that has been engineered to display the Lassa virus glycoprotein complex on its surface, allowing a single shot to train the immune system against both pathogens. Critically, the vaccine can be freeze-dried, which could allow it to be distributed in regions where maintaining a continuous cold chain is difficult — a significant practical advantage for many Lassa-endemic areas.
In the randomized, controlled phase 1 trial, 54 healthy adult volunteers in the Baltimore area received two doses of LASSARAB at varying strengths, formulated with an adjuvant, 28 days apart; a comparison group received a licensed rabies vaccine alone. Through 61 days of follow-up, no serious adverse events were reported, and side effects were generally mild and short-lived. After two doses, all 44 evaluable LASSARAB recipients developed a Lassa virus antibody response, compared with none of the control group. Rabies antibody responses reached full seroconversion and protective neutralizing-antibody levels across all groups, including controls, meeting the World Health Organization’s established correlate of protection for rabies. Notably, protection in animal studies of LASSARAB appeared to depend on non-neutralizing, antibody-mediated immune functions rather than classic neutralizing antibodies — a mechanism consistent with what’s been observed in human Lassa fever survivors, and one that distinguishes this vaccine’s underlying biology from that of some competing Lassa vaccine candidates built on live, replicating platforms.
The trial is ongoing, with safety and immune durability being tracked through 394 days post-vaccination. If those longer-term results remain favorable, researchers plan to advance the candidate into larger, more advanced clinical trials.
Thermostability and a warming, shifting risk map
The development matters for global health security largely because of two converging factors: where the disease is headed, and how the vaccine could actually reach people. Climate-driven ecological shifts are expected to expand the range of the rodent reservoir species that spread Lassa virus, pushing the disease well beyond its historical footprint in Nigeria and West Africa. UMSOM Dean Mark T. Gladwin noted that these environmental changes could put an estimated 700 million people at risk worldwide, with the number of African countries developing ecological conditions suitable for Lassa virus spread potentially rising sharply by 2070 — a trajectory that outpaces the reach of current surveillance and health infrastructure in many of the regions likely to be newly affected.
That expanding risk map makes the vaccine’s physical properties as important as its immunology. LASSARAB can be freeze-dried, meaning it does not require the uninterrupted cold-chain storage that limits many vaccines, including some competing Lassa candidates built on live viral platforms. In regions where refrigerated storage and transport are unreliable or unavailable — often the same low-resource areas where Lassa virus is endemic or newly emerging — a thermostable product is far more likely to actually get into arms.
The study was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Sources and further reading:
First-in-Human Clinical Trial Has Promising Results for New Lassa Fever Vaccine – University of Maryland Baltimore
NIH-Funded Researchers Share Early Results of Lassa Fever Vaccine in Phase 1 Clinical Trial – Thomas Jefferson University
Ortiz, J.R., Kurup, D., Kaufman, A.C. et al. Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial. Nature Medicine, 9 June 2026.