Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). A genome-wide CRISPR screen using IFN alpha-treated Huh7.5 cells was performed to determine which ISGs were required in order for host cells to suppress yellow fever virus (YFV) infection.
Project description:Mechanisms of poor responses to vaccines remain unknown. Yellow fever-naïve adults were vaccinated with a yellow fever vaccine (YF-17D, Stamaril). Transcriptomic profilling of blood collected pre-vaccination and post-vaccination (day 3, 7, 14 and 84) was performed in order to identify candidate biomarkers of antibody response to the vaccine.
Project description:Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, depends on the availablity of a high-quality genome assembly. Here we use DNA proximity ligaton (Hi-C) and Pacific Biosciences long reads to create AaegL5 - a highly contiguous A. aegypti reference.
Project description:To better understand how innate immunity to vaccination can lead to lasting protective immunity, we have used systemic bioinformatics approaches to define the signature of the yellow fever specific immune response in a cohort of 21 volunteers.
Project description:The immune response to vaccines is critically dependent on multiple host and environmental factors including acute and chronic infections as well as metabolic and/or pathophysiological states of the host. In this study, we used computational systems biology to analyze a cohort of Ugandan subjects following immunization with the Yellow Fever vaccine (YF-17D) to identify pre-vaccination molecular and cellular mechanisms that are associated with the response to the vaccine. By integrating gene expression profiling, cell subset phenotyping and cytokine measurements, we highlight the upregulated levels of interferon-regulated, and inflammasome genes and proteins at the time of vaccination as negative correlates of the antibody response to the YF-17D vaccine. We show that this innate immune response is associated with higher levels of genes that interact with bacterial components and with increased frequencies of Tr1 CD39+ IL-10 producing cells. Our results provide a framework to define the influence of environmental parameters present prior to vaccination on the response to vaccines in human populations