IAVI's Lassa Fever Vaccine Shows Promising Safety and Immune Response in Phase 1 Trial
核心洞察
IAVI (搜索)'s rVSVΔG-LASV-GPC vaccine candidate demonstrated acceptable safety profile and elicited robust, long-lasting immune responses in a Phase 1 trial with 114 participants from the U.S. and Liberia.
The single-dose vaccine produced cross-reactive antibodies against multiple Lassa virus lineages circulating in West Africa, with no serious adverse events or hearing loss reported during 12-month follow-up.
Results published in the New England Journal of Medicine support advancement to an ongoing Phase 2a trial in West Africa, making this the most advanced Lassa fever (搜索) vaccine in clinical development.
A Lassa fever (搜索) vaccine candidate developed by the International AIDS Vaccine Initiative (IAVI (搜索)) has demonstrated encouraging safety and immunogenicity results in a Phase 1 clinical trial, bringing hope for protection against a deadly viral hemorrhagic disease that claims thousands of lives annually in West Africa.
The trial results, published in the New England Journal of Medicine, show that rVSVΔG-LASV-GPC produced robust and durable immune responses in healthy adults while maintaining an acceptable safety profile. The study enrolled 114 volunteers from sites in the United States and Liberia, with participants monitored for 12 months following vaccination.
Trial Design and Participants
The Phase 1 trial, designated IAVI (搜索) C102, was conducted from July 2021 through December 2023 across multiple sites including the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) at Redemption Hospital, Brigham and Women's Hospital, East-West Medical Research Institute, and George Washington University School of Medicine and Health Sciences.
Participants were randomly assigned in a 4:1 ratio to receive the vaccine candidate at one of four dose levels or placebo. The study included 44 participants from the United States and 60 from Liberia, with one group invited to receive a second dose 6 to 20 weeks after the initial vaccination.
Safety Profile and Immune Response
The vaccine demonstrated a favorable safety profile, causing only transient local reactions, primarily tenderness and pain at the injection site, and systemic effects such as malaise. Notably, no serious adverse events were reported, including hearing loss, which is a known risk of Lassa virus infection. Reactogenicity was lower in Liberian participants compared to those in the United States.
"No vaccine-related serious adverse events and no cases of hearing loss – a known risk of LASV infection – were reported during this study," the researchers noted.
Analysis of immune responses revealed robust and long-lasting cellular and humoral responses across all dose levels, persisting up to 12 months post-vaccination. Importantly, antibodies induced by vaccination were cross-reactive to other Lassa virus lineages known to circulate across West Africa, suggesting potential for broad protection from a single vaccine.
The study found that a second dose provided no appreciable benefit to humoral or cellular responses, supporting the single-dose regimen. No infectious vaccine virus particles were detected in plasma, urine, or saliva samples.
Platform Technology and Development
The rVSVΔG-LASV-GPC vaccine is based on a replication-competent recombinant vesicular stomatitis virus (搜索)-vectored platform encoding a Lassa virus glycoprotein complex (搜索). This platform is the same technology used for ERVEBO, Merck (搜索)'s licensed Ebola virus vaccine that was approved by the FDA in 2019 and has been extensively used during Ebola outbreaks in adults and children across more than a dozen countries.
IAVI (搜索) licensed the vaccine technology from the Public Health Agency of Canada, where it was developed by scientists at the National Microbiology Laboratory. The vaccine is based on an attenuated strain of vesicular stomatitis virus (搜索) that has been modified to express a Lassa virus protein essential for viral infection.
Addressing an Urgent Medical Need
Lassa fever (搜索) represents a significant public health threat in West Africa, where it is endemic in Guinea, Liberia, Mali, Nigeria, and Sierra Leone. The disease is estimated to cause 100,000 to 300,000 infections annually, including 5,000 to 10,000 deaths, though the true public health impact remains unknown due to underreporting and limited surveillance.
"A vaccine is urgently needed as shifting patterns in climate, migration, and human-animal interaction may expand Lassa's footprint across West Africa and even further afield," said Swati Gupta, DrPH, MPH, Vice President and head of emerging infectious diseases and epidemiology at IAVI (搜索).
The World Health Organization has included Lassa virus in its Pathogens Prioritization framework as a priority pathogen needing urgent research and development, and as a prototype pathogen for the Arenavirus family. It is also a priority target for the Coalition for Epidemic Preparedness Innovations (CEPI), which funded the clinical trial.
Clinical Development Progress
Based on the strength of preclinical and Phase 1 clinical data, rVSVΔG-LASV-GPC has advanced to an ongoing IAVI (搜索)-sponsored Phase 2a clinical trial supported by CEPI in West Africa. This makes it currently the most advanced Lassa virus vaccine candidate in the clinical development pipeline.
Dr. Kent Kester, Executive Director of Vaccine R&D at CEPI, emphasized the significance of these results: "The promising Phase 1 data for IAVI (搜索)'s vaccine candidate takes us one step closer towards a much-needed Lassa fever (搜索) vaccine which, if successful, could save thousands of lives and avert millions of dollars of societal costs in the West African countries that bear the burden of this disease."
Regional Support and Future Outlook
The vaccine development effort has gained significant regional support. In September 2025, West African Ministers of Health and the West African Health Organization endorsed a communiqué at the Lassa fever (搜索) International Conference in Abidjan, Côte d'Ivoire, reaffirming their political endorsement of accelerating Lassa fever vaccine readiness as a regional strategic health priority.
The ministers committed to supporting IAVI (搜索)'s vaccine development through collaborative co-funding and joint action to mobilize resources. IAVI has committed to advancing the vaccine to licensure and ensuring affordable access should it prove safe and efficacious in clinical trials.
The trial was funded by CEPI and the U.S. National Institute of Allergy and Infectious Diseases, with additional support from the European & Developing Countries Clinical Trials Partnership. The research represents a collaborative effort involving investigators from the United States, United Kingdom, and Liberia, with immune response analysis conducted by scientists at Imperial College London.