A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge
العنوان: | A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge |
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المؤلفون: | 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 |
المصدر: | Pathogens Volume 8 Issue 3 Pathogens, Vol 8, Iss 3, p 133 (2019) |
بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | 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 |
الوصف: | 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. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 2076-0817 |
DOI: | 10.3390/pathogens8030133 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5f8deb0d8e4133b9e4c51e0399d060a |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....a5f8deb0d8e4133b9e4c51e0399d060a |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20760817 |
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DOI: | 10.3390/pathogens8030133 |