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

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 vacci...

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Main Authors: Julian Rothen, Carl Murie, Jason Carnes, Atashi Anupama, Salim Abdulla, Mwajuma Chemba, Maxmillian Mpina, Marcel Tanner, B Kim Lee Sim, Stephen L Hoffman, Raphael Gottardo, Claudia Daubenberger, Ken Stuart
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199392&type=printable
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author Julian Rothen
Carl Murie
Jason Carnes
Atashi Anupama
Salim Abdulla
Mwajuma Chemba
Maxmillian Mpina
Marcel Tanner
B Kim Lee Sim
Stephen L Hoffman
Raphael Gottardo
Claudia Daubenberger
Ken Stuart
author_facet Julian Rothen
Carl Murie
Jason Carnes
Atashi Anupama
Salim Abdulla
Mwajuma Chemba
Maxmillian Mpina
Marcel Tanner
B Kim Lee Sim
Stephen L Hoffman
Raphael Gottardo
Claudia Daubenberger
Ken Stuart
author_sort Julian Rothen
collection DOAJ
description 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.
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spelling doaj.art-8e8d2c41a2a54c209bbc05676e6efe802025-02-27T05:34:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019939210.1371/journal.pone.0199392Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.Julian RothenCarl MurieJason CarnesAtashi AnupamaSalim AbdullaMwajuma ChembaMaxmillian MpinaMarcel TannerB Kim Lee SimStephen L HoffmanRaphael GottardoClaudia DaubenbergerKen StuartMalaria 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199392&type=printable
spellingShingle Julian Rothen
Carl Murie
Jason Carnes
Atashi Anupama
Salim Abdulla
Mwajuma Chemba
Maxmillian Mpina
Marcel Tanner
B Kim Lee Sim
Stephen L Hoffman
Raphael Gottardo
Claudia Daubenberger
Ken Stuart
Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
PLoS ONE
title Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
title_full Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
title_fullStr Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
title_full_unstemmed Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
title_short Whole blood transcriptome changes following controlled human malaria infection in malaria pre-exposed volunteers correlate with parasite prepatent period.
title_sort whole blood transcriptome changes following controlled human malaria infection in malaria pre exposed volunteers correlate with parasite prepatent period
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199392&type=printable
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