Disruption of plasmepsin-4 and merozoites surface protein-7 genes in Plasmodium berghei induces combined virulence-attenuated phenotype
Open Access
- 18 July 2011
- journal article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 1 (1), 39
- https://doi.org/10.1038/srep00039
Abstract
Blood stage malaria parasites causing a mild and self limited infection in mice have been obtained with either radiation or chemical mutagenesis showing the possibility of developing an attenuated malaria vaccine. Targeted disruption of plasmepsin-4 (pm4) or the merozoite surface protein-7 (msp7) genes also induces a virulence-attenuated phenotype in terms of absence of experimental cerebral malaria (ECM), delayed increase of parasitemia and reduced mortality rate. The decrease in virulence in parasites lacking either pm4 or msp7 is however incomplete and dependent on the parasite and mouse strain combination. The sequential disruption of both genes induced remarkable virulence-attenuated blood-stage parasites characterized by a self-resolving infection with low levels of parasitemia and no ECM. Furthermore, convalescent mice were protected against the challenge with P. berghei or P. yoelii parasites for several months. These observations provide a proof-of-concept step for the development of human malaria vaccines based on genetically attenuated blood-stage parasites.This publication has 60 references indexed in Scilit:
- Systematic Genetic Analysis of the Plasmodium falciparum MSP7-Like Family Reveals Differences in Protein Expression, Location, and Importance in Asexual Growth of the Blood-Stage ParasiteEukaryotic Cell, 2010
- Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental MalariaThe American Journal of Pathology, 2010
- IP-10-Mediated T Cell Homing Promotes Cerebral Inflammation over Splenic Immunity to Malaria InfectionPLoS Pathogens, 2009
- Deletion of the Plasmodium falciparum Merozoite Surface Protein 7 Gene Impairs Parasite Invasion of ErythrocytesEukaryotic Cell, 2008
- Truncation of Plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage developmentMolecular and Biochemical Parasitology, 2008
- Chemical Attenuation of Plasmodium berghei Sporozoites Induces Sterile Immunity in MiceInfection and Immunity, 2008
- Plasmodium falciparumduring pregnancy: a puzzling parasite tissue adhesion tropismParasitology, 2007
- A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral MalariaThe American Journal of Pathology, 2007
- Plasmodium yoelii Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against InfectionInfection and Immunity, 2007
- A family affair: var genes, PfEMP1 binding, and malaria diseaseCurrent Opinion in Microbiology, 2006