Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection

Background: Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. Methods: We used chimeric Ifnar<sup>...

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Main Authors: Lisa Oestereich, Helena Müller-Kräuter, Elisa Pallasch, Thomas Strecker
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/7/1436
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author Lisa Oestereich
Helena Müller-Kräuter
Elisa Pallasch
Thomas Strecker
author_facet Lisa Oestereich
Helena Müller-Kräuter
Elisa Pallasch
Thomas Strecker
author_sort Lisa Oestereich
collection DOAJ
description Background: Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. Methods: We used chimeric Ifnar<sup>−/−</sup> C57BL/6 (Ifnar<sup>−/− Bl6</sup>) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes. Results: Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%. Conclusions: Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.
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spelling doaj.art-86aff6124d8a4bd8aee511aa912407922023-11-18T21:43:41ZengMDPI AGViruses1999-49152023-06-01157143610.3390/v15071436Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus InfectionLisa Oestereich0Helena Müller-Kräuter1Elisa Pallasch2Thomas Strecker3Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, GermanyInstitute of Virology, Philipps University Marburg, 35043 Marburg, GermanyDepartment of Virology, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, GermanyInstitute of Virology, Philipps University Marburg, 35043 Marburg, GermanyBackground: Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. Methods: We used chimeric Ifnar<sup>−/−</sup> C57BL/6 (Ifnar<sup>−/− Bl6</sup>) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes. Results: Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%. Conclusions: Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.https://www.mdpi.com/1999-4915/15/7/1436Lassa mammarenavirusLassa feverarenavirusvirus-like particleneutralizing antibodiesin vivo protection
spellingShingle Lisa Oestereich
Helena Müller-Kräuter
Elisa Pallasch
Thomas Strecker
Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
Viruses
Lassa mammarenavirus
Lassa fever
arenavirus
virus-like particle
neutralizing antibodies
in vivo protection
title Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
title_full Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
title_fullStr Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
title_full_unstemmed Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
title_short Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection
title_sort passive transfer of animal derived polyclonal hyperimmune antibodies provides protection of mice from lethal lassa virus infection
topic Lassa mammarenavirus
Lassa fever
arenavirus
virus-like particle
neutralizing antibodies
in vivo protection
url https://www.mdpi.com/1999-4915/15/7/1436
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