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Virus–Host Interactions Involved in Lassa Virus Entry and Genome Replication
Open AccessArticle

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

1
Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA
2
GeoVax, Inc., Smyrna, GA 30080, USA
3
Office of Technology Licensing and Commercialization, Georgia State University, Atlanta, GA 30303, USA
4
Department of Biology, Georgia State University, Atlanta, GA 30302, USA
*
Author to whom correspondence should be addressed.
Contributed equally to this work.
Pathogens 2019, 8(3), 133; https://doi.org/10.3390/pathogens8030133
Received: 17 July 2019 / Revised: 23 August 2019 / Accepted: 25 August 2019 / Published: 28 August 2019
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+ and CD8+ 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. View Full-Text
Keywords: Lassa vaccine; replication-deficient MVA vector; VLP formation; single-dose efficacy; cell-mediated immunity Lassa vaccine; replication-deficient MVA vector; VLP formation; single-dose efficacy; cell-mediated immunity
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Salvato, M.S.; Domi, A.; Guzmán-Cardozo, C.; Medina-Moreno, S.; Zapata, J.C.; Hsu, H.; McCurley, N.; Basu, R.; Hauser, M.; Hellerstein, M.; Guirakhoo, F. A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge. Pathogens 2019, 8, 133.

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