A National Institutes of Health (NIH)-sponsored clinical trial for a promising Lassa fever vaccine candidate has begun enrolling participants at the University of Maryland School of Medicine in Baltimore. The Phase 1 trial marks the first human testing of LASSARAB, a dual-purpose vaccine designed to protect against both Lassa fever and rabies.
Lassa fever, a viral hemorrhagic disease endemic to West Africa, can be fatal and causes permanent hearing loss in approximately one-third of those infected. Currently, no specific treatments or vaccines exist for this serious illness, which is primarily spread by multimammate rats native to the region and can also transmit from person to person.
"The candidate vaccine being tested in this trial was developed by an NIH-supported research team at Thomas Jefferson University in Philadelphia," said NIAID Director Jeanne Marrazzo, M.D., M.P.H. "The progression of this candidate from the lab to a first-in-humans clinical trial is a promising step towards a vaccine to prevent Lassa fever."
Trial Design and Participant Information
The Phase 1 trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), will evaluate the safety and immunogenicity of the LASSARAB vaccine in up to 55 healthy adults aged 18 to 50 years. Participants will be administered two injections 28 days apart, receiving either the vaccine candidate at one of three different concentrations or an FDA-licensed rabies vaccine as a control.
The study design aims to determine the optimal dosage that balances safety with immune response, a critical step in vaccine development. Participants will be closely monitored for adverse reactions and immune response to both the Lassa virus and rabies components of the vaccine.
Promising Preclinical Results
The advancement to human trials follows compelling preclinical research published in 2024 by Matthias Schnell, Ph.D., and colleagues at Thomas Jefferson University. Their studies demonstrated that two doses of LASSARAB, administered 28 days apart, provided complete protection to nonhuman primates exposed to large, lethal amounts of Lassa virus six weeks after the second inoculation.
"The preclinical data showed remarkable efficacy," explained Dr. Schnell in a statement about the research. "All immunized animals survived exposure to Lassa virus, which is particularly encouraging given the severity of the challenge dose used in our studies."
Innovative Vaccine Technology
LASSARAB represents an innovative approach to vaccine development, utilizing a platform based on a weakened (attenuated) rabies vaccine that is subsequently inactivated. The experimental vaccine is engineered to express all standard rabies proteins along with a Lassa virus surface protein called the glycoprotein precursor complex (GPC).
This dual-purpose design could potentially provide protection against both diseases with a single vaccine regimen, offering significant public health benefits in regions where both viruses circulate. If successful in clinical trials and approved by the FDA, LASSARAB could become an important tool in preventing two serious infectious diseases.
Public Health Significance
Lassa fever affects an estimated 100,000 to 300,000 people annually in West Africa, with approximately 5,000 deaths. The disease is particularly prevalent in Nigeria, Sierra Leone, Guinea, and Liberia, where multimammate rats frequently come into contact with human dwellings.
Dr. Marrazzo emphasized the importance of this research: "Developing effective countermeasures against Lassa fever is a public health priority, especially as climate change and human population growth may expand the geographic range of the host rodents and increase human exposure to the virus."
The lack of current treatment options makes prevention through vaccination particularly important. Early symptoms of Lassa fever often resemble those of other common illnesses, making diagnosis difficult without specialized laboratory testing that is often unavailable in endemic regions.
Next Steps and Future Outlook
If this initial Phase 1 trial demonstrates that LASSARAB is safe and generates robust immune responses to both the Lassa virus and rabies components, the vaccine will advance to further clinical testing to evaluate its protective efficacy.
The trial is registered on clinicaltrials.gov under the identifier NCT06546709, where additional information about the study protocol and enrollment criteria can be found.
NIAID continues to support research on Lassa fever and other emerging infectious diseases as part of its mission to develop better means of preventing, diagnosing, and treating infectious and immune-mediated diseases worldwide.
