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Preclinical Safety Assessment of the EBS-LASV Vaccine Candidate against Lassa Fever Virus

Authors :
Demetrius Matassov
Lisa Evans DeWald
Stefan Hamm
Rebecca M. Nowak
Cheryl S. Gerardi
Theresa E. Latham
Rong Xu
Amara Luckay
Tracy Chen
Marc Tremblay
Jeffry Shearer
Melissa Wynn
John H. Eldridge
Kelly Warfield
Kevin Spurgers
Source :
Vaccines, Vol 12, Iss 8, p 858 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene. Preclinical studies were performed to evaluate EBS-LASV’s neurovirulence potential following intracranial (IC) injection and to determine the biodistribution and vector replication following intramuscular (IM) inoculation in mice. In addition, the potential EBS-LASV toxicity was assessed using repeated-dose IM EBS-LASV administration to rabbits. All mice receiving the IC injection of EBS-LASV survived, while mice administered the unattenuated control vector did not. The vaccine was only detected in the muscle at the injection site, draining lymph nodes, and the spleen over the first week following IM EBS-LASV injection in mice, with no detectable plasma viremia. No toxicity was observed in rabbits receiving a three-dose regimen of EBS-LASV. These studies demonstrate that EBS-LASV is safe when administered to animals and supported a first-in-human dose-escalation, safety, and immunogenicity clinical study.

Details

Language :
English
ISSN :
2076393X
Volume :
12
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.5ac6e9310ddd44a58999bee90fd7b27a
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines12080858