A lipid nanoparticle-formulated self-amplifying RNA rift valley fever vaccine induces a robust humoral immune response in mice
Author(s)
Type
Journal Article
Abstract
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality rates in ruminants and sometimes severe to fatal complications like encephalitis and hemorrhagic fever in humans. There is no licensed RVF vaccine for human use while approved livestock vaccines have suboptimal safety or efficacy. We designed self-amplifying RNA (saRNA) RVF vaccines and assessed their humoral immunogenicity in mice. Plasmid DNA encoding the Rift Valley fever virus (RVFV) medium (M) segment consensus sequence (WT consensus) and its derivatives mutated to enhance cell membrane expression of the viral surface glycoproteins n (Gn) and c (Gc) were assessed for in vitro expression. The WT consensus and best-expressing derivative (furin-T2A) were cloned into a Venezuelan equine encephalitis virus (VEEV) plasmid DNA replicon and in vitro transcribed into saRNA. The saRNA was formulated in lipid nanoparticles and its humoral immunogenicity in BALB/c mice was assessed. High quantities of dose-dependent RVFV Gn IgG antibodies were detected in the serum of all mice immunized with either WT consensus or furin-T2A saRNA RVF vaccines. Significant RVFV pseudovirus-neutralizing activity was induced in mice immunized with 1 µg or 10 µg of the WT consensus saRNA vaccine. The WT consensus saRNA RVF vaccine warrants further development.
Date Issued
2024-10-01
Date Acceptance
2024-09-10
Citation
Vaccines, 2024, 12 (10)
ISSN
2076-393X
Publisher
MDPI AG
Journal / Book Title
Vaccines
Volume
12
Issue
10
Copyright Statement
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39460255
PII: vaccines12101088
Subjects
G(N)
GLYCOPROTEINS
Immunology
Life Sciences & Biomedicine
lipid nanoparticles
Medicine, Research & Experimental
Research & Experimental Medicine
Rift Valley fever virus
RVF vaccine
RVFV
saRNA
Science & Technology
self-amplifying RNA
TAILS
VEEV
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
1088
Date Publish Online
2024-09-24