Helena Müller
Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity
Müller, Helena; Fehling, Sarah Katharina; Dorna, Jens; Urbanowicz, Richard A.; Oestereich, Lisa; Krebs, Yvonne; Kolesnikova, Larissa; Schauflinger, Martin; Krähling, Verena; Magassouba, N’Faly; Fichet-Calvet, Elisabeth; Ball, Jonathan K.; Kaufmann, Andreas; Bauer, Stefan; Becker, Stephan; von Messling, Veronika; Strecker, Thomas
Authors
Sarah Katharina Fehling
Jens Dorna
Richard A. Urbanowicz
Lisa Oestereich
Yvonne Krebs
Larissa Kolesnikova
Martin Schauflinger
Verena Krähling
N’Faly Magassouba
Elisabeth Fichet-Calvet
JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology
Andreas Kaufmann
Stefan Bauer
Stephan Becker
Veronika von Messling
Thomas Strecker
Abstract
Lassa mammarenavirus (LASV) is a rodent-borne arenavirus endemic to several West African countries. It is the causative agent of human Lassa fever, an acute viral hemorrhagic fever disease. To date, no therapeutics or vaccines against LASV have obtained regulatory approval. Polyclonal neutralizing antibodies derived from hyperimmunized animals may offer a useful strategy for prophylactic and therapeutic intervention to combat human LASV infections. The LASV envelope surface glycoprotein complex (GP) is the major target for neutralizing antibodies, and it is the main viral antigen used for the design of an LASV vaccine. Here, we assessed the immunogenic potential of mammalian cell-derived virus-like particles (VLPs) expressing GP from the prototypic LASV strain Josiah in a native-like conformation as the sole viral antigen. We demonstrate that an adjuvanted prime-boost immunization regimen with GP-derived VLPs elicited neutralizing antibody responses in rabbits, suggesting that effective antigenic epitopes of GP were displayed. Notably, these antibodies exhibited broad reactivity across five genetic lineages of LASV. VLP-based immunization strategies may represent a powerful approach for generating polyclonal sera containing cross-reactive neutralizing antibodies against LASV.
Citation
Müller, H., Fehling, S. K., Dorna, J., Urbanowicz, R. A., Oestereich, L., Krebs, Y., …Strecker, T. (2020). Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity. npj Vaccines, 5, Article 71. https://doi.org/10.1038/s41541-020-00219-x
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 10, 2020 |
Online Publication Date | Aug 4, 2020 |
Publication Date | Aug 4, 2020 |
Deposit Date | Aug 17, 2020 |
Publicly Available Date | Mar 29, 2024 |
Journal | npj Vaccines |
Electronic ISSN | 2059-0105 |
Peer Reviewed | Peer Reviewed |
Volume | 5 |
Article Number | 71 |
DOI | https://doi.org/10.1038/s41541-020-00219-x |
Public URL | https://nottingham-repository.worktribe.com/output/4816399 |
Publisher URL | https://www.nature.com/articles/s41541-020-00219-x |
Additional Information | Received: 29 January 2020; Accepted: 10 July 2020; First Online: 4 August 2020; : The authors declare no competing interests. |
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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