A candidate vaccine against Lassa fever has shown a strong safety profile and encouraging immune responses in a phase 1 clinical trial, raising hopes for a long-sought preventive tool against the viral disease endemic in parts of West Africa. The vaccine, a replication-competent recombinant vesicular stomatitis virus-vectored formulation encoding the Lassa virus glycoprotein complex (rVSVΔG-LASV-GPC), was tested in 114 healthy volunteers in the United States and Liberia. Researchers reported no vaccine-related serious adverse events and no cases of hearing loss, a known complication of Lassa fever.
The randomized trial enrolled 53 participants in the US and 61 in Liberia. Volunteers received either a single intramuscular dose of the vaccine at varying concentrations or a placebo, while a smaller group received two high-dose injections several weeks apart. Participants were monitored for up to 12 months to assess safety and immune responses.
Given Lassa fever’s association with sensorineural hearing loss, investigators closely tracked changes in hearing before and after vaccination. No new hearing impairment of 30 decibels or more was detected among vaccine recipients.
Immunogenicity results were particularly encouraging. A single vaccine dose triggered Lassa virus–specific IgG antibody responses in 98% of US participants and 92% of Liberian participants, with antibodies showing cross-reactivity across multiple viral lineages. Neutralizing antibodies were observed in nearly all US recipients and in three-quarters of Liberian recipients.
Vaccine-specific T-cell responses were also detected by day 29 in all tested US participants. Although transient, dose-related systemic reactions were reported, particularly at the highest dose, these effects resolved within days. At that dose, 26% of US participants experienced grade 3 reactions, but none were serious.
Summarizing the findings, the study authors wrote: “In findings consistent with those of preclinical studies that were conducted during the development of the human vaccine candidate and with the rVSVΔG-LASV-GPC research vaccine, the vaccine resulted in transient local and systemic reactogenicity events but no serious adverse events or hearing loss.”
The trial was led by Elissa Malkin, DO, of the Vaccine Research Unit at George Washington University, and the results were published online on November 05, 2025, in The New England Journal of Medicine.
Researchers cautioned that, as a phase 1 study, the trial was not designed for hypothesis testing and involved a relatively small sample size. Some participants were lost to follow-up, and preexisting antibodies among some Liberian volunteers may have influenced immune responses.
The study was funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health. Several authors reported financial relationships with funders, research organizations, or pharmaceutical companies, and one author disclosed a patent filing.
