Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1168054 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Live-attenuated viral vaccines have been successfully used to combat infectious disease for decades but due to their empirical derivation, little is known about their mechanisms of attenuation. This lack of understanding makes the development of next generation live attenuated vaccines difficult. The success of the 17D vaccine and availability of the parent virus, Asibi, makes it an excellent model to understand the molecular basis of attenuation of a live attenuated vaccine and the effects of viral diversity on vaccine function. Due to the differences in genetic diversity between WT Asibi virus and its 17D vaccine derivative, we investigated the changes in genetic diversity of 17D and Asibi viruses following treatment with ribavirin.
2020-01-01 | E-MTAB-8504 | biostudies-arrayexpress
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:Chikungunya virus fidelity-variant live-attenuated vaccine
| PRJNA639833 | ENA
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. 27 RNA sampes from Human PBMC exposed to Lassa and Mop/Las (see below): 1 uninf. PBMC 4hr, 8 hr, 24 hr 2 LASV PBMC 4hr, 8 hr, 24 hr X 3 3 ML29 PBMC 4hr, 8 hr, 24 hr There are 3 biological replicates of this experiment in that the PBMC of 3 different individuals have been used.
2013-11-05 | E-GEOD-41300 | biostudies-arrayexpress
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
Project description:PBMC-derived CD8 T cell activation and gene expression profiles were assessed 14 days following a single dose of a candidate live-attenuated tetravalent denge virus vaccine (DENVax). Three distinct populations of CD8+ T cells were isolated by flow cytometric sorting: 1) CD3+ CD8+ CD38- HLA-DR- T cells, 2) CD3+ CD8+ CD38+ HLA-DR+ T cells, and 3) CD3+ CD8+ CD71+ HLA-DR+ T cells
2019-08-05 | GSE132950 | 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. 30 RNA samples from Monkey PBMC: 4 uninf. Monkey PBMC, 8 SIV-infected Monkey PBMC(From 8 Monkeys), 5 SIV+ML29-sc infected week1(Monkey PBMC), 5 SIV+ML29-sc infected week2(Monkey PBMC), 1 SIV+ML29-ig infected week1(Monkey PBMC), 1 SIV+ML29-ig infected week2(Monkey PBMC), 2 SIV+Arm-sc infected week1(Monkey PBMC), 2 SIV+Arm-sc infected week2(Monkey PBMC), 1 only ML29-iv infected week1(Monkey PBMC), 1 only ML29-iv infected week2(Monkey PBMC)
2013-11-04 | E-GEOD-33687 | biostudies-arrayexpress
Project description:Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identified pre-vaccination mechanisms predictive of broad antibody responses after immunization with a tetravalent live-attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways including TGF-b signaling expressed by CD68low monocytes and the metabolokines phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were positively correlated with broadly neutralizing Ab responses against DENV. In contrast expression of pro-inflammatory pathways and cytokines (IFN, IL-1) in CD68hi monocytes and primary and secondary bile acids negatively correlated with broad DENVDENV specific Ab responses. Induction of TGF-b and IFNs respectively by PC/PE and bile acids in CD68low and CD68hi monocytes and their impact on viral sensing was confirmed in vitro. We show that the balance between metabolites and pro- or anti-inflammatory innate immune cells drives broad and protective B cell response to the live-attenuated dengue vaccine.
2023-07-27 | GSE209760 | GEO
Project description:Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. Live attenuated vaccines have been successfully used to combat infection by flaviviruses, such as yellow fever and Japanese encephalitis viruses. A Zika virus harboring combined mutations in the envelope protein glycosylation site and in the nonstructural 4B protein amino acid 36 (ZE4B-36) was generated and assessed for stability, attenuation, and protection against infection. To determine the genetic stability of its RNA genome, ZE4B-36 was serially passaged in vitro in Vero cells. Virus harvested from passages (P)1 to P6 was subjected to next generation sequencing and downstream analysis to determine its nucleotide sequence variability. Specifically, single nucleotide variant analysis showed that the ZE4B-36 genome decreased its genetic diversity and resulted in a more stable nucleotide sequence. Thus, in addition to showing attenuation and protection, ZE4B-36 is a stable live attenuated virus that possesses characteristics important for a vaccine to combat Zika disease.
2021-12-31 | E-MTAB-9496 | biostudies-arrayexpress