LASSARAB Phase 1 Trial: Dual Lassa-Rabies Vaccine Shows 100% Seroconversion and Favorable Safety Profile
Key Insights
An interim analysis of the first-in-human Phase 1 trial of LASSARAB, an inactivated rabies (search)-vectored Lassa fever (search) vaccine, demonstrated 100% seroconversion against both Lassa virus and rabies virus by day 61 in healthy adults.
The vaccine was well tolerated across all dose groups, with no serious adverse events or grade ≥3 reactions; solicited symptoms were predominantly mild and self-limited.
All LASSARAB recipients achieved rabies (search)-neutralizing antibody titers exceeding the WHO correlate of protection (≥0.5 IU/ml), matching responses seen with licensed rabies vaccines.
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 two-in-one vaccine designed to protect against Lassa fever (search) and rabies (search) in a single formulation. The findings, published in Nature Medicine, show that the adjuvanted inactivated rabies-vectored vaccine was well tolerated and induced robust immune responses against both viruses in healthy adult volunteers.
The trial, featured as one of Nature Medicine's "Eleven clinical trials that will shape medicine in 2026," enrolled 54 healthy adults aged 18–50 at the University of Maryland School of Medicine's Center for Vaccine Development and Global Health. Enrollment occurred from January 22 to April 22, 2025, with the interim analysis extending through June 24, 2025.
Dual-Threat Disease Burden
Lassa fever (search), caused by Lassa virus, is a severe hemorrhagic disease endemic to parts of West Africa, causing an estimated 300,000 to 500,000 infections and over 5,000 deaths annually. The disease can lead to severe complications including organ failure, hearing loss, and long-term neurological disorders. Currently, no licensed vaccines exist to prevent Lassa fever. Rabies (search) remains a major public health challenge in many of the same West African countries where Lassa virus is endemic, with control hindered by low vaccination coverage in dogs, shortages of human vaccines, and weak infrastructure for post-exposure prophylaxis.
Vaccine Platform and Trial Design
LASSARAB is based on an inactivated rabies (search) virus vector engineered to express the Lassa virus glycoprotein complex (GPC) (search), formulated with a synthetic adjuvant (aPHAD-SE). Among the three Lassa fever (search) vaccines currently under development, LASSARAB is the only candidate based on a killed or attenuated virus. The platform leverages the rabies vaccine's long-established safety record, enduring immunity, existing manufacturing infrastructure, and global distribution networks.
In this randomized Phase 1 dose-escalation trial, participants were split into four groups: group A received 700 rU of antigen with 5 µg of adjuvant; group B received 1,400 rU with 5 µg; group C received two concurrent injections totaling 2,800 rU and 10 µg; and group D received the licensed inactivated rabies (search) vaccine (Imovax Rabies, Sanofi Pasteur) as a control. Vaccines were administered intramuscularly on days 1 and 29.
Safety Profile
Across all vaccine dose groups, no serious adverse events, no new-onset chronic medical conditions, and no potential immune-mediated conditions were observed. Reported side effects—including injection-site tenderness (72.7% after dose 1), injection-site pain (68.2%), malaise (43.2%), myalgia (38.6%), and headache (25.0%)—were temporary and resolved without additional treatment. All solicited events were self-limited, predominantly mild (grade 1), and there were no severe (grade 3) or higher events.
"These results provide the first clinical evidence that a rabies (search)-vectored platform can safely generate immunity to Lassa virus in humans," said 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 Sidney Kimmel Medical College at Thomas Jefferson University.
Robust Immunogenicity
By day 61 after the first dose, 100% of LASSARAB recipients developed Lassa virus-specific antibodies, while all control participants did not. LASV-GPC serum IgG geometric mean titers (GMTs) reached 158.8 IU/ml (95% CI 81.1–310.9) in group A, 135.4 IU/ml (95% CI 87.6–209.3) in group B, and 331.0 IU/ml (95% CI 174.0–629.6) in group C, compared to 1.5 IU/ml (95% CI 0.7–3.2) in the control group.
Simultaneously, all participants receiving LASSARAB achieved levels of neutralizing antibody against rabies (search) virus that exceeded the World Health Organization's established threshold for protection (≥0.5 IU/ml). By day 61, rabies-neutralizing GMTs were 7.7 IU/ml (95% CI 5.3–11.1) in group A, 7.2 IU/ml (95% CI 5.0–10.5) in group B, and 12.3 IU/ml (95% CI 9.3–16.2) in group C, compared to 16.7 IU/ml (95% CI 9.2–30.3) in the control group. From day 36 through day 61, seroprotection was 100% across all groups.
A strong correlation was observed between rabies (search) glycoprotein IgG ELISA titers and neutralizing antibody titers measured by RFFIT (Spearman's ρ = 0.89; 95% CI 0.86–0.91; P < 0.001), suggesting ELISA may serve as a reliable surrogate for neutralization assays in future development.
Preclinical Foundation and Comparative Context
The clinical results are supported by preclinical data in which two intramuscular doses of LASSARAB adjuvanted with a TLR-4 agonist protected all vaccinated nonhuman primates (NHPs) from lethal Lassa virus challenge. Protection occurred despite the absence of pre-challenge Lassa-neutralizing antibodies, consistent with observations from human Lassa survivors, and was associated with non-neutralizing antibodies with Fcγ receptor-mediated effector functions.
Among the three Lassa vaccine candidates in clinical development, LASSARAB is the only non-replicating platform. The replication-competent rVSV-based LASV vaccine has demonstrated efficacy in NHP challenge models but is not licensed for use in pregnant women or children under 12 months and requires ultra-cold storage (−80°C to −60°C). The measles-vectored LASV vaccine, also live-attenuated, is not recommended during pregnancy or in severely immunosuppressed individuals. In contrast, inactivated rabies (search) vaccines have been administered to millions globally with a well-documented safety record, including in pregnant and immunocompromised persons, and can be lyophilized for thermostable storage.
"The ability to combine protection against Lassa fever (search) and rabies (search) in a single vaccine could have a substantial public-health impact in regions where both diseases remain endemic," Schnell noted.
Limitations and Next Steps
As a Phase 1 trial, the study was not powered for confirmatory hypothesis testing, and all statistical inferences are exploratory. Enrollment was limited to healthy younger adults in a region where neither Lassa fever (search) nor rabies (search) is prevalent, which may limit generalizability to endemic populations. Follow-up is currently limited to 61 days; longer-term data including antibody durability through day 394, cross-lineage immune responses, and additional immunologic characterization will be needed.
The final study report will include serious adverse events and adverse events of special interest through day 394, as well as exploratory antibody responses at days 121 and 394. If efficacy is confirmed in larger trials, this combination vaccine could help protect populations from two priority pathogens and have a meaningful public health impact in regions where both diseases remain major threats.