IAVI: Lassa Virus Vaccine Development
- Ray Sullivan
- Apr 13
- 3 min read
Lassa fever is a serious zoonotic hemorrhagic disease caused by the Lassa virus, an enveloped RNA virus in the Arenaviridae family. It is endemic in multiple countries in West Africa, where its primary reservoir is the multi-mammate rat. The geographic range of the animal host places large populations at risk of infection, with some estimates of up to four million infections per year, and this is projected to increase substantially due to the influence of land use, climate change, and population growth. Additionally, there is the threat of the Lassa virus being used for bioterrorism.
A group led by IAVI in Jersey City, NJ, pursued the preclinical development of a promising Lassa fever vaccine candidate, which has advanced into Phase 1 and 2 human clinical trials. The vaccine utilizes a vesicular stomatitis virus (VSV) vector where the VSV glycoprotein (G) is replaced with the Lassa virus glycoprotein complex (GPC). Preclinical studies in cynomolgus macaques demonstrated that a single intramuscular injection of the clinical vaccine candidate provided complete protection against a lethal Lassa virus challenge. Vaccination elicited both humoral (GPC-binding and neutralizing antibodies) and cellular (IFN-γ secreting T cells) immune responses. The elicited neutralizing antibodies showed activity against GPCs from diverse Lassa virus lineages, suggesting broad protective potential. Transcriptomic analysis revealed an early innate immune response signature consistent with other VSV-based vaccines. These robust preclinical findings strongly support the ongoing clinical evaluation of the vaccine as a potential prophylactic vaccine against Lassa fever.
The successful preclinical development of VSVΔG-LASV-GPC represents a significant step forward in the search for an effective Lassa fever vaccine.
The demonstration of complete protection in a non-human primate model with a single low dose is highly encouraging for human applications.
The induction of broadly neutralizing antibodies suggests the potential for protection against diverse circulating Lassa virus strains, which is crucial for a globally effective vaccine.
The similarities in the early transcriptomic response to the licensed Ebola vaccine further support this VSV-based platform’s safety and immunogenicity profile.
IAVI is a non-profit that develops vaccines and antibodies for HIV, tuberculosis, and other emerging infectious diseases. In February 2025, it inaugurated its newly relocated Vaccine Design and Development Laboratory at 95 Greene Street in Jersey City, New Jersey, transitioning from its previous base at the Brooklyn Army Terminal. This state-of-the-art facility serves as the preclinical development hub for IAVI's emerging infectious disease vaccine portfolio, focusing on pathogens such as Lassa virus, Sudan virus, and Marburg virus. The Vaccine Design and Development Laboratory specializes in the recombinant vesicular stomatitis virus (rVSV) vaccine platform, the same technology utilized in Merck's ERVEBO®, a licensed Ebola vaccine. The Jersey City lab is a 350,000-square-foot facility near the Hudson River waterfront.
Cooper CL, Morrow G, Yuan M, Postler TS, Neal ML, Cross RW, Woolsey C, Agans KN, Borisevich V, McNamara RP, Atyeo C, Roy V, Germosen D, Hou F, Li SL, Reiserova L, Choi Y, Wilson A, Wagner D, Wallace-Selman O, Carpov A, Geng F, Frederick DJ, DeStefano J, Ercolini AM, Enriquez AS, Hastie KM, Ramos da Silva S, Sayeed E, Coleman JW, Kilianski A, Alter G, Saphire EO, Aitchison JD, Geisbert TW, Gupta SB, Feinberg MB, Parks CL. Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trials. EBioMedicine. 2025 Apr;114:105647. doi: 10.1016/j.ebiom.2025.105647. Epub 2025 Mar 28. PMID: 40157130.
Comments