Journal article

Controlled human malaria infection with Plasmodium falciparum demonstrates impact of naturally acquired immunity on virulence gene expression

Anna Bachmann, Ellen Bruske, Ralf Krumkamp, Louise Turners, J Stephan Wichers, Michaels Petter, Jana Held, Michael F Duffy, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner, Bertrand Lell, Thomas Laystsen, Matthias Frank, Benjamin Mordmueller, Egbert Tannich

PLoS Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

The pathogenesis of Plasmodium falciparum malaria is linked to the variant surface antigen PfEMP1, which mediates tethering of infected erythrocytes to the host endothelium and is encoded by approximately 60 var genes per parasite genome. Repeated episodes of malaria infection result in the gradual acquisition of protective antibodies against PfEMP1 variants. The antibody repertoire is believed to provide a selective pressure driving the clonal expansion of parasites expressing unrecognized PfEMP1 variants, however, due to the lack of experimental in vivo models there is only limited experimental evidence in support of this concept. To get insight into the impact of naturally acquired immuni..

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Grants

Awarded by Federal Ministry of Education and Research of the German Centre for Infection Research (DZIF)


Awarded by German Research Foundation (DFG)


Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health under SBIR


Awarded by EDCTP strategic primer grant


Awarded by German Federal Ministry of Education and Research (BMBF)


Awarded by Danish Council for Independent Research


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

BM, PGK, and AB received funding for the clinical trial and the var gene expression analysis by the Federal Ministry of Education and Research in the framework of the German Centre for Infection Research (DZIF) (TTU 03.702 Clinical Trial Platform and TTU 03.703 Clinical Research Group) (http://www.dzif.de/).AB and JSW were funded by the German Research Foundation (DFG) grant BA 5213/3-1. Production of PfSPZ Challenge (NF54) by SLH was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (https://www.niaid.nih.gov/) under SBIR award numbers 5R44AI058375 and 5R44AI055229. Slide reading training was provided through the EDCTP strategic primer grant SP. 2011.41304.062 (http://www.edctp.org/).MF and EB were funded by the German Federal Ministry of Education and Research (BMBF) grant 01KA110 (https://www.bmbf.de/), TL and LT by the Novo Nordisk Fonden (https://novonordiskfonden.dk/da/) and Danish Council for Independent Research (https://ufm.dk/en) (4004-00624B). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.