Comparison of the human blood transcriptomic profile during the natural Yellow Fever infection and the Yellow Fever 17D vaccine

Abstract

Yellow Fever (YF) is a viral disease caused by the Yellow Fever virus (YFV). The treatment is supportive, and prevention is through mosquito control measures and vaccination with the Yellow Fever vaccine, YFV-17D. The YFV-17D is one of the most effective vaccines ever developed, providing 30-35 years of immunization with a single dose. Few studies have been conducted to investigate the immune response of the YFV-17D vaccine. Among them, two meta-analyses were conducted: one to identify differentially expressed lncRNAs (DELs) and another to compare the transcriptome of 13 different vaccines. The second meta-analysis was conducted by the research group of BEPE's supervisor, Thomas Hagan, and observed peculiar immune responses elicited by the YFV-17D vaccine compared to the other vaccines studied. Among the peculiarities, it was observed an early activation of T and B cells on Day 1 post-vaccination and a delayed interferon response that peaked on Day 7. Based on this, our aim is to conduct a meta-analysis to better investigate the immune response of the YFV-17D vaccine using transcriptome data from human blood. We will identify meta-differentially expressed genes (meta-DEGs) and construct a meta-gene coexpression network. Additionally, we will compare the results of the meta-analysis of the YFV-17D vaccine with the transcriptome data from the human blood of naturally infected YFV patients previously analyzed during the Ph.D. project of the student. By combining the knowledge of the Brazilian research group of YFV infection with the expertise of the BEPE's supervisor group, which is a specialist in systems vaccinology and has conducted studies on the YFV-17D vaccine, we aim to bring more clarity to the biological mechanisms involved in the immune responses of this highly effective vaccine. In this sense, the insights generated by the proposed project could drive the development of vaccines with improved efficacy. (AU)