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The effect of dosage on the protective efficacy of whole-sporozoite formulation...

Moita, Diana; Rôla, Catarina; Nunes-Cabaço, Helena; Nogueira, Gonçalo; Maia, Teresa G.; Othman, Ahmad Syibli; Franke-Fayard, Blandine; Janse, Chris J.

Immunization with Plasmodium sporozoites, either attenuated or administered under the cover of an antimalarial drug, can induce strong protection against malaria in pre-clinical murine models, as well as in human trials. Previous studies have suggested that whole-sporozoite (WSpz) formulations based on parasites with longer liver stage development induce higher protection, but a comparative analysis of four dif...


A genetically modified Plasmodium berghei parasite as a surrogate for whole-spo...

Moita, Diana; Maia, Teresa G.; Duarte, Miguel; Andrade, Carolina M.; Albuquerque, Inês S.; Dwivedi, Ankit; Silva, Joana C.; González-Céron, Lilia

Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages, is a promising strategy for immunization against malaria and several PfWSp-based vaccine candidates are currently undergo...


Generation of a genetically modified chimeric plasmodium falciparum parasite ex...

Miyazaki, Yukiko; Marin-Mogollon, Catherin; Imai, Takashi; Mendes, António M.; van der Laak, Rianne; Sturm, Angelika; Geurten, Fiona J. A.

Chimeric rodent malaria parasites with the endogenous circumsporozoite protein (csp) gene replaced with csp from the human parasites Plasmodium falciparum (Pf) and P. vivax (Pv) are used in preclinical evaluation of CSP vaccines. Chimeric rodent parasites expressing PfCSP have also been assessed as whole sporozoite (WSP) vaccines. Comparable chimeric P. falciparum parasites expressing CSP of P. vivax could be u...


Translational control of UIS4 protein of the host-parasite interface is mediate...

Silva, Patrícia A. G. C.; Guerreiro, Ana; Santos, Jorge M.; Braks, Joanna A. M.; Janse, Chris J.; Mair, Gunnar

UIS4 is a key protein component of the host-parasite interface in the liver stage of the rodent malaria parasite Plasmodium berghei and required for parasite survival after invasion. In the infectious sporozoite, UIS4 protein has variably been shown to be translated but also been reported to be translationally repressed. Here we show that uis4 mRNA translation is regulated by the P. berghei RNA binding protein ...


The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete mor...

Santos, Jorge M.; Kehrer, Jessica; Franke-Fayard, Blandine; Frischknecht, Friedrich; Janse, Chris J.; Mair, Gunnar

The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host c...


Universal features of post-transcriptional gene regulation are critical for pla...

Mair, Gunnar R.; Lasonder, Edwin; Garver, Lindsey S.; Franke-Fayard, Blandine M. D.; Carret, Céline K.; Wiegant, Joop C. A. G.; Dirks, Roeland W.

A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the molecular machinery involved in the silencing of transcri...


Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer lon...

Douradinha, Bruno; van Dijk, Melissa R.; Ataíde, Ricardo; van Gemert, Geert-Jan; Thompson, Joanne; Franetich, Jean-François; Mazier, Dominique

Immunisation with live, radiation-attenuated sporozoites (RAS) or genetically attenuated sporozoites (GAS) of rodent plasmodial parasites protects against subsequent challenge infections. We recently showed that immunisation with Plasmodium berghei GAS that lack the microneme protein P36p protects mice for a period of up to 4 months. Here, we show that the period of full protection induced by p36p(-)-sporozoite...


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