Clinical Trial Begins for Lassa Fever Vaccine Candidate
Researchers at the University of Maryland School of Medicine (UMSOM) have launched a Phase 1 clinical trial to evaluate the safety and immunogenicity of LASSARAB, a novel vaccine candidate designed to protect against Lassa fever. The study, registered at ClinicalTrials.gov (NCT06546709), marks a significant step in addressing the Lassa virus, a zoonotic pathogen that causes severe hemorrhagic fever in West Africa. The trial compares the experimental vaccine, which uses a modified rabies virus vector, against the licensed Imovax Rabies vaccine.
How the LASSARAB Vaccine Works
LASSARAB is a monovalent vaccine engineered to express both the rabies virus glycoprotein and the full Lassa virus glycoprotein (LASV-GPC). According to the University of Maryland Center for Vaccine Development and Global Health, the vaccine uses a genetically modified rabies virus backbone derived from the SAD B19 strain. To improve safety, developers incorporated an arginine-to-glutamate substitution at amino acid position 333, a modification specifically intended to reduce the vector’s neurotropism. The vaccine is administered with an adjuvant, aPHAD-SE, which is a synthetic monophosphoryl lipid A analog formulated in a squalene-based nanoemulsion to boost the immune response.
Trial Design and Participant Safety
The trial is a randomized, dose-escalation study involving healthy adults aged 18 to 50. Investigators assigned participants to one of four groups, with three receiving varying doses of LASSARAB plus the adjuvant, and a control group receiving the standard-of-care rabies vaccine. To maintain the integrity of the study, researchers utilized a double-blinded approach where participants and most study staff remained unaware of specific vaccine assignments. The trial protocol includes rigorous safety monitoring, including tablet-based audiometry to screen for potential sensorineural hearing loss, a known complication associated with Lassa fever infection. Safety oversight is provided by an independent Safety Monitoring Committee (SRC) and an Independent Safety Monitor (ISM).
Comparing LASSARAB to Existing Standards
The trial utilizes the licensed Imovax Rabies vaccine as a comparator, which is a human diploid cell vaccine (HDCV) produced by Sanofi Pasteur. While HDCV is an established, FDA-approved vaccine for rabies, its use here serves as a baseline for comparing the reactogenicity and immune response of the Lassa-targeted vector. The following table summarizes the primary objectives of the ongoing study:
| Objective | Measurement Method |
|---|---|
| Safety and Reactogenicity | Monitoring of local and systemic adverse events through 7 days post-vaccination. |
| Immune Response (LASV) | Geometric mean IgG titers and seroconversion rates via ELISA. |
| Immune Response (RABV) | Neutralizing antibody titers measured by Rapid Fluorescent Focus Inhibition Test (RFFIT). |
Why This Research Matters
Lassa fever remains a public health priority due to its high morbidity and mortality rates in endemic regions. According to the World Health Organization (WHO), Lassa fever is estimated to cause 100,000 to 300,000 infections annually in West Africa, with approximately 5,000 deaths. Unlike other viral hemorrhagic fevers, there is currently no widely available, licensed vaccine for Lassa fever. By leveraging a proven rabies vector platform, researchers aim to create a stable, effective immunization strategy that could eventually be deployed in regions where Lassa virus transmission is frequent. The current study is expected to provide critical data on the safety profile and the durability of the immune response through day 394 of the follow-up period.