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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Veröffentlicht in:Pathogens (Basel) Jg. 8; H. 3; S. 133
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 28.08.2019
MDPI
Schlagworte:
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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Zusammenfassung: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.
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Contributed equally to this work.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens8030133