This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Lassa virus (LASV), an Old World Arenavirus and the etiological agent of Lassa hemorrhagic fever (LHF), causes up to 300,000 annual infections in West Africa. Approximately 30% of infections result in disease varying from mild influenza-like illness to lethal LHF causing several thousand deaths per year. The large disease burden, severe complications, lethality and the possibility that LASV can be used as a biological warfare agent make a strong case for effective vaccine development. A ML29 Lassa fever vaccine candidate carrying mutated major structural proteins of LASV and RdRp of non-pathogenic Mopeia is attenuated in guinea pigs and rhesus macaques. We have shown that ML29 vaccine protects guinea pigs from lethal infection with homologous and heterologous LASV strains. Here we report the efficacy of the vaccine in nonhuman primates. Six Marmosets (Callithrix jacchus) were vaccinated with 1000 PFU of ML29 and challenged on day 30 with lethal dose of LASV-Josiah. A second group of marmosets (n=4), the unvaccinated control group, was infected with the same dose of LASV. Animals were observed for clinical signs of disease and blood was collected for hematology and blood chemistry. LASV infection induced weight loss, fever, high viremia and viral burden in tissues, elevated liver enzymes, decreased levels of albumin in plasma, and severe morbidity 15-20 days after infection in non vaccinated animals. Prominent histopathology findings included hepatic necrosis and immunophenotypic alterations of cells in target tissues confirming immunosuppressive phenotype of fatal human LHF. In contrast, vaccinated marmosets survived after challenge with no clinical manifestations while hematology and biochemical parameters were normal. Importantly, plasma samples collected 16, 21, and 28 days after challenge had no detectable levels of LASV. This work confirms the ML29 efficacy, safety and immunogenicity data previously obtained in the strain 13 guinea pig model of LHF.
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