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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Vydané v:	Pathogens (Basel) Ročník 8; číslo 3; s. 133
Hlavní autori:	Salvato, Maria S., Domi, Arban, Guzmán-Cardozo, Camila, Medina-Moreno, Sandra, Zapata, Juan Carlos, Hsu, Haoting, McCurley, Nathanael, Basu, Rahul, Hauser, Mary, Hellerstein, Michael, Guirakhoo, Farshad
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland MDPI AG 28.08.2019 MDPI
Predmet:	Animals Antibodies Antigens CD4 antigen CD8 antigen Cell culture cell-mediated immunity Dengue hemorrhagic fever Epidemics Fatalities Fever Genomes Glycoproteins Immunogenicity Lassa fever Lassa vaccine Lethal dose Lymphocytes Lymphocytes T Mathematical analysis Matrix protein Nosocomial infections Proteins Public health replication-deficient MVA vector RNA polymerase single-dose efficacy Survival analysis Vaccines Vector-borne diseases Viral diseases Virus-like particles Viruses VLP formation Liberia Turkey Mali West Africa Ankara Turkey Sierra Leone Nigeria replication-deficient MVA vector VLP formation Lassa vaccine single-dose efficacy cell-mediated immunity
ISSN:	2076-0817, 2076-0817
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Contributed equally to this work.
ISSN:	2076-0817 2076-0817
DOI:	10.3390/pathogens8030133