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

Author:

Müller Helena,Fehling Sarah Katharina,Dorna Jens,Urbanowicz Richard A.ORCID,Oestereich Lisa,Krebs YvonneORCID,Kolesnikova Larissa,Schauflinger Martin,Krähling Verena,Magassouba N’Faly,Fichet-Calvet Elisabeth,Ball Jonathan K.,Kaufmann Andreas,Bauer Stefan,Becker Stephan,von Messling VeronikaORCID,Strecker ThomasORCID

Abstract

AbstractLassa 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.

Funder

Deutsche Forschungsgemeinschaft

Jürgen-Manchot-Stiftung and the MArburg Research Academy

RCUK | Medical Research Council

Leibniz-Gemeinschaft

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology

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