Lassa mammarenavirus strain:Mopeia-Lassa 29
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ABSTRACT:
PROVIDER: PRJNA73681 | ENA |
REPOSITORIES: ENA
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Project description:Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
2023-02-21 | GSE225258 | GEO
Project description:The virulent Lassa fever virus (LASV) and the non-pathogenic Mopeia virus (MOPV) infect rodents and incidentally people in West Africa. The mechanism of LASV damage in human beings is unclear. A live-attenuated reassortant of MOPV and LASV protects rodents and primates from Lassa fever disease. Peripheral blood mononuclear cells from healthy human subjects were expose to either LASV or ML29 in order to identify early cellular responses that could be attributed to the difference in virulence between both viruses. Differential expression of interferon-related genes as well as coagulation-related genes could lead to an explanation for Lassa fever pathogenesis and lead to protective treatments for Lassa fever disease.
2013-11-05 | GSE41300 | GEO
Project description:Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We compared the efficacy of measles-based and Mopeia-based vaccine platforms against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from Lassa virus infection and disease after a single immunization but with different efficacy. Analyses of immune responses demonstrated that complete protection was associated with early and robust T-cell responses against LASV but not humoral responses nor neutralizing antibodies. Transcriptomic and proteomic analyses performed during the immunization phase confirmed the role of early innate immunity and T-cell priming in vaccine efficacy and showed specific profiles detectable as early as two days after immunization. The most efficient candidate, measles vector expressing simultaneously LASV glycoprotein and nucleoprotein, will be soon evaluated in phase I clinical trial.
2019-06-20 | GSE132998 | GEO
Project description:Lassa fever (LF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs of virulent disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of AIDS. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, weight loss, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections included increased expression of interferon response genes and decreased expression of COX2, IL-1?, coagulation intermediates and nuclear receptors needed for stress signaling. Here it is demonstrated that SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and that none developed signs of arenavirus disease or persistence. Furthermore, 5 of 5 animals given a heterologous challenge with a lethal dose of LCMV-WE survived without developing disease signs.
2013-11-04 | GSE33687 | GEO