A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
| Autor: | Sandra Medina-Moreno, Farshad Guirakhoo, Camila Guzmán-Cardozo, Rahul Basu, Arban Domi, Hao-Ting Hsu, Maria S. Salvato, Mary J Hauser, Juan C. Zapata, Nathanael McCurley, Michael Hellerstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Microbiology (medical)
single-dose efficacy Modified vaccinia Ankara viruses lcsh:Medicine Biology medicine.disease_cause Virus Article Dengue fever 03 medical and health sciences replication-deficient MVA vector medicine Immunology and Allergy cell-mediated immunity Lassa fever Molecular Biology 030304 developmental biology 0303 health sciences VLP formation General Immunology and Microbiology 030306 microbiology Immunogenicity Lethal dose lcsh:R medicine.disease Virology 3. Good health Lassa vaccine Hemorrhagic Fevers Infectious Diseases Lassa virus |
| Zdroj: | Pathogens Volume 8 Issue 3 Pathogens, Vol 8, Iss 3, p 133 (2019) |
| ISSN: | 2076-0817 |
| DOI: | 10.3390/pathogens8030133 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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