Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period

• Published in: PloS one 2018-06, Vol.13 (6), p.e0199392-e0199392
• Main Authors: Rothen, Julian, Murie, Carl, Carnes, Jason, Anupama, Atashi, Abdulla, Salim, Chemba, Mwajuma, Mpina, Maxmillian, Tanner, Marcel, Lee Sim, B Kim, Hoffman, Stephen L, Gottardo, Raphael, Daubenberger, Claudia, Stuart, Ken
• Format: Article
• Language: English
• Subjects: Adults; Bioinformatics; Biology; Biology and Life Sciences; Blood; Blood Proteins - genetics; Cell cycle; Cryopreservation; Erythrocytes; Gene expression; Gene Expression Profiling; Gene Expression Regulation - genetics; Gene regulation; Genes; Genetic aspects; Genomes; Humans; Immunology; Infections; Infectious diseases; Inoculation; Insecticides; Liver; Malaria; Malaria, Falciparum - blood; Malaria, Falciparum - genetics; Malaria, Falciparum - parasitology; Medical research; Medicine and Health Sciences; Molecular chains; Parasitemia; Parasitemia - blood; Parasitemia - genetics; Parasites; Parasitology; Peripheral blood; Phosphatidylinositol; Plasmodium falciparum; Plasmodium falciparum - isolation & purification; Plasmodium falciparum - pathogenicity; Prevention; Public health; Ribonucleic acid; RNA; RNA sequencing; Secondary analysis; Sporozoites; Studies; Transcription; Transcriptome - genetics; Vaccine efficacy; Vaccines; Vector-borne diseases; Volunteers
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0199392

Malaria continues to be one of mankind's most devastating diseases despite the many and varied efforts to combat it. Indispensable for malaria elimination and eventual eradication is the development of effective vaccines. Controlled human malaria infection (CHMI) is an invaluable tool for vaccine efficacy assessment and investigation of early immunological and molecular responses against Plasmodium falciparum infection. Here, we investigated gene expression changes following CHMI using RNA-Seq. Peripheral blood samples were collected in Bagamoyo, Tanzania, from ten adults who were injected intradermally (ID) with 2.5x104 aseptic, purified, cryopreserved P. falciparum sporozoites (Sanaria® PfSPZ Challenge). A total of 2,758 genes were identified as differentially expressed following CHMI. Transcriptional changes were most pronounced on day 5 after inoculation, during the clinically silent liver phase. A secondary analysis, grouping the volunteers according to their prepatent period duration, identified 265 genes whose expression levels were linked to time of blood stage parasitemia detection. Gene modules associated with these 265 genes were linked to regulation of transcription, cell cycle, phosphatidylinositol signaling and erythrocyte development. Our study showed that in malaria pre-exposed volunteers, parasite prepatent period in each individual is linked to magnitude and timing of early gene expression changes after ID CHMI.