TOPLINE:

The Lassa fever vaccine candidate — a replication-competent recombinant vesicular stomatitis virus-vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex (rVSVΔG-LASV-GPC) — demonstrated a favorable safety profile, with no cases of hearing loss, and induced robust immune responses to major LASV lineages.

METHODOLOGY:

• Researchers conducted a phase 1 randomized clinical trial to assess the safety and immunogenicity of the Lassa fever vaccine rVSVΔG-LASV-GPC in 114 healthy participants: 53 in the US (median age, 26 years; 22 male) and 61 in Liberia (median age, 24 years; 29 male).
• Participants received either a single intramuscular vaccine dose of 2 × 10⁴, 2 × 10⁵, 2 × 10⁶, or 2 × 10⁷ plaque-forming units (PFUs) or placebo; some received two vaccine doses of 2 × 10⁷ PFUs or placebo given 6-20 weeks apart. All were followed up for 12 months after administration.
• The primary objective was to evaluate the safety and side-effect profile of rVSVΔG-LASV-GPC across different dose levels.
• Because Lassa fever is associated with sensorineural hearing loss, participants were assessed for new hearing loss of ≥ 30 dB before and after vaccination.
• Secondary objectives included the assessment of LASV GPC-specific immunoglobulin G (IgG) responses, Lassa fever-specific T-cell responses, and the distribution of rVSVΔG-LASV-GPC in plasma, urine, and saliva.

TAKEAWAY:

• No vaccine-associated serious adverse events or hearing loss occurred. Transient, dose-dependent systemic reactogenicity events were seen among vaccine recipients; at the highest dose, 26% of US participants experienced grade 3 events, which were resolved within days.
• A single dose at all dose levels induced robust LASV GPC-specific IgG responses in 98% of US recipients and 92% of Liberian recipients, with cross-reactivity across multiple LASV lineages.
• Serum neutralizing antibody responses were observed in 98% of US recipients and 75% of Liberian recipients.
• Vaccine-specific T-cell responses were detected by day 29 in all US participants who were tested; no infectious vaccine virus particles were detected in any RNA-positive plasma samples.

IN PRACTICE:

“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 authors of the study wrote.

SOURCE:

The study was led by Elissa Malkin, DO, Vaccine Research Unit, George Washington University, Washington DC. It was published online on November 05, 2025, in The New England Journal of Medicine.

LIMITATIONS:

As a phase 1 trial, the study did not include hypothesis testing and had a relatively small sample size. Several US participants were lost to follow-up, and some Liberian participants had preexisting antibodies to LASV, which may have influenced the results.

DISCLOSURES:

The study was supported by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. Some authors disclosed receiving grants, contracts, consulting fees or other financial relationships with study funders, various organizations, and pharmaceutical companies; one author had filed for a patent.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.