T Cell Regulatory and Suppression Mechanisms in Malaria

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

In unpublished work: We conducted a longitudinal, randomized, open-label study in healthy Malian children in an area of intense seasonal malaria transmission, and found that presumptive antimalarial treatment decreased patent parasitemia through the dry season but did not modulate fold change in PD1-expressing CD4 and CD8 T cells in children or adults. In children but not adults, presumptive treatment led to lower fold change in FOXP3-expressing CD4 T cells. Fold change of immune cell subsets varied across dry and rainy seasons, but these changes followed distinct patterns in children and adults. The manuscript describing this work is nearing submission. We conducted a meta-analysis of transcriptomic data from three independent Sanaria® PfSPZ Vaccine trials and found that Vδ2 cells expand during PfSPZ Vaccine administration and predict sterile immunity. We performed whole blood RNA sequencing on 48 subjects from three PfSPZ Vaccine trials to better define protective PfSPZ cellular responses. Using 144 published RNAseq datasets spanning 27 sorted human immune cell subsets, we associated genes to cell type of highest expression to create canonical cell-type transcriptomes, then mapped differentially expressed genes in protected or unprotected PfSPZ Vaccine recipients to canonical cell types. Using a novel computational analysis of transcriptomes, we identified a NKG2A+ subset of Vδ2 cells that expand in response to PfSPZ Vaccine and associate with sterile immunity. The manuscript describing this work is in progress.