An investigational vaccine for the Lassa fever virus (Josiah strain) vectored with inactivated rabies has demonstrated clinically significant immunogenicity against both viruses and a favorable safety profile in a first-in-human, phase 1 clinical trial conducted by the Center for Vaccine Development (CVD) and Global Health, University of Maryland School of Medicine (UMSOM).1
"Climate change is causing Lassa fever to extend its reach far beyond its Nigerian and West African origins, putting an estimated 700 million people at risk worldwide," said UMSOM Dean Mark Gladwin, MD in a statementreleased on the publication of the trial interim results.2
"By 2070, the number of countries across Africa that will develop ecological conditions suitable for Lassa virus spread could drastically increase, so a vaccine to prevent this deadly infection is desperately needed," Gladwin remarked.
Although the current Ebola outbreak in West Africa, exacerbated by late response and lack of vaccine for the circulating species, requires all possible measures, Lassa fever is another zoonotic viral hemorrhagic illness in the region that is a priority target of the World Health Organization (WHO). It is estimated to infect 300,000 people and kill 5,000 each year, with an 80% mortality of mother or fetus when contracted in late-term pregnancy, and with no vaccine yet available.3
Vaccine development has been confounded by incomplete information about the immune mechanism responses to the Lassa fever virus, according to Justin Ortiz, MD, MS, CVD and Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, UMSOM, and colleagues.
"Humoral and cell-mediated responses have been identified among human survivors of severe Lassa fever, but there is no immune correlate of protection. Convalescent serum from survivors has not proven effective in clinical studies," they recount.
Scientists at Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA were, however, able to exploit the observation that survivors typically exhibit an early, high-titer IgG response to the viral glycoprotein complex (GPC), which mediates cellular entry. Survivors also generated strong T cell responses against GPC and the viral nucleoprotein, while demonstrating low systemic inflammation.Their investigational adjuvanted inactivated rabies virus-vectored Lassa virus vaccine (LASSARAB) expresses both the rabies and Lassa virus GPC.
"This platform incorporates the rabies virus glycoprotein, which could simultaneously confer immunity to rabies and thereby enhance the feasibility and public health value of a combination vaccine in endemic regions," Ortiz and colleagues explain.They also note that the investigational vaccine can be freeze-dried for storage, which would facilitate its distribution in regions where it is difficult to maintain cold chains.
What You Need to Know
In this first-in-human phase 1 trial, 100% of participants who received two doses achieved more than a fourfold increase in antibodies against both the Lassa virus glycoprotein complex and rabies glycoprotein, regardless of dose level.
Most adverse events were mild and self-limited, supporting continued clinical development as researchers evaluate long-term durability and safety through nearly 13 months of follow-up.
By combining protection against Lassa fever and rabies in a freeze-dried formulation that is easier to store and distribute, LASSARAB may improve vaccine access in resource-limited regions where both diseases remain significant health concerns.
In the phase 1 clinical trial, 54 healthy adult participants were randomized to receive either two intramuscular doses of LASSARAB separated by 28 days containing 700 (n=15), 1400 (n=15), or 28,00 (n=14) relative units of antigen formulated with the TLR-4 agonist 3D-6acylPHAD-SE adjuvant, or the licensed rabies vaccine as a control (n=10).The primary measures were immunogenicity and safety, with this first publication from the study reporting measures through day 61.The study will follow-up on both durability of response and safety through day 394.
Ortiz and colleagues reported that after two doses of LASSARAB, seroconversion of Lassa virus GPC IgG and rabies glycoprotein IgG (on Enzyme-Linked Immunosorbent Assay [ELISA]) increased over fourfold for 100% of the recipients, regardless of dose.The control group exhibited that response only to the rabies. Adverse events across the cohort were characterized as predominantly mild and self limited.
"This vaccine is designed to protect against two viruses of global health importance," Ortiz stated."By combining targets into a single product, it could reduce the need for separate vaccination efforts and streamline delivery in settings where access is limited."2
References
1. Ortiz JR, Kurup D, Kaufman AC, et al. Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial. Nat Med. 2026, published online June 9. ttps://doi.org/10.1038/s41591-026-04429-z
