Analysis of Gene Expression Profiles to study Malaria Vaccine Dose Efficacy & Immune Response Modulation

Abstract

AbstractMalaria is a life-threatening disease, and the Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of the different vaccination doses on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on 275 and 583 samples collected from the GEO datasets. At first, exploratory data analysis based Principal component analysis (PCA) shown the distinct pattern of different doses. Subsequently, differential gene expression analysis using edgeR revealed the significantly (FDR <0.005) 158 down-regulated and 61 upregulated genes between control vs. Controlled Human Malaria Infection (CHMI) samples. Further, enrichment analysis of significant genes using Annotation and GAGE tools delineate the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc.,genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight to the dual role of cytokine responses in malaria pathogenesis and variations in their expression patterns after various doses of vaccination involved in protection.