A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge

A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization,...

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Main Authors: Maria S. Salvato, Arban Domi, Camila Guzmán-Cardozo, Sandra Medina-Moreno, Juan Carlos Zapata, Haoting Hsu, Nathanael McCurley, Rahul Basu, Mary Hauser, Michael Hellerstein, Farshad Guirakhoo
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Pathogens
Subjects:
Lassa vaccine
replication-deficient MVA vector
VLP formation
single-dose efficacy
cell-mediated immunity
Online Access:https://www.mdpi.com/2076-0817/8/3/133
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spelling doaj-a806c794d0394737b02bd7f860aa634a2020-11-25T02:01:02ZengMDPI AGPathogens2076-08172019-08-018313310.3390/pathogens8030133pathogens8030133A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus ChallengeMaria S. Salvato0Arban Domi1Camila Guzmán-Cardozo2Sandra Medina-Moreno3Juan Carlos Zapata4Haoting Hsu5Nathanael McCurley6Rahul Basu7Mary Hauser8Michael Hellerstein9Farshad Guirakhoo10Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USAGeoVax, Inc., Smyrna, GA 30080, USAInstitute of Human Virology, University of Maryland, Baltimore, MD 21201, USAInstitute of Human Virology, University of Maryland, Baltimore, MD 21201, USAInstitute of Human Virology, University of Maryland, Baltimore, MD 21201, USAInstitute of Human Virology, University of Maryland, Baltimore, MD 21201, USAOffice of Technology Licensing and Commercialization, Georgia State University, Atlanta, GA 30303, USADepartment of Biology, Georgia State University, Atlanta, GA 30302, USAGeoVax, Inc., Smyrna, GA 30080, USAGeoVax, Inc., Smyrna, GA 30080, USAGeoVax, Inc., Smyrna, GA 30080, USALassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.https://www.mdpi.com/2076-0817/8/3/133Lassa vaccinereplication-deficient MVA vectorVLP formationsingle-dose efficacycell-mediated immunity
collection DOAJ
language English
format Article
sources DOAJ
author Maria S. Salvato
Arban Domi
Camila Guzmán-Cardozo
Sandra Medina-Moreno
Juan Carlos Zapata
Haoting Hsu
Nathanael McCurley
Rahul Basu
Mary Hauser
Michael Hellerstein
Farshad Guirakhoo
spellingShingle Maria S. Salvato
Arban Domi
Camila Guzmán-Cardozo
Sandra Medina-Moreno
Juan Carlos Zapata
Haoting Hsu
Nathanael McCurley
Rahul Basu
Mary Hauser
Michael Hellerstein
Farshad Guirakhoo
A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
Pathogens
Lassa vaccine
replication-deficient MVA vector
VLP formation
single-dose efficacy
cell-mediated immunity
author_facet Maria S. Salvato
Arban Domi
Camila Guzmán-Cardozo
Sandra Medina-Moreno
Juan Carlos Zapata
Haoting Hsu
Nathanael McCurley
Rahul Basu
Mary Hauser
Michael Hellerstein
Farshad Guirakhoo
author_sort Maria S. Salvato
title A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
title_short A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
title_full A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
title_fullStr A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
title_full_unstemmed A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
title_sort single dose of modified vaccinia ankara expressing lassa virus-like particles protects mice from lethal intra-cerebral virus challenge
publisher MDPI AG
series Pathogens
issn 2076-0817
publishDate 2019-08-01
description Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.
topic Lassa vaccine
replication-deficient MVA vector
VLP formation
single-dose efficacy
cell-mediated immunity
url https://www.mdpi.com/2076-0817/8/3/133
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