A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites.

Autor:	van Schaijk BC; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Ploemen IH; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Annoura T; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center, Leiden, Netherlands., Vos MW; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Foquet L; Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium., van Gemert GJ; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Chevalley-Maurel S; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center, Leiden, Netherlands., van de Vegte-Bolmer M; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Sajid M; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center, Leiden, Netherlands., Franetich JF; Centre d'Immunologie et des Maladies Infectieuses, Université Pierre et Marie Curie-Paris 6, Paris, France., Lorthiois A; Centre d'Immunologie et des Maladies Infectieuses, Université Pierre et Marie Curie-Paris 6, Paris, France., Leroux-Roels G; Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium., Meuleman P; Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium., Hermsen CC; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Mazier D; Centre d'Immunologie et des Maladies Infectieuses, Université Pierre et Marie Curie-Paris 6, Paris, France., Hoffman SL; Sanaria Inc., Rockville, United States., Janse CJ; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center, Leiden, Netherlands., Khan SM; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center, Leiden, Netherlands., Sauerwein RW; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2014 Nov 19; Vol. 3. Date of Electronic Publication: 2014 Nov 19.
DOI:	10.7554/eLife.03582
Abstrakt:	A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine.
Databáze:	MEDLINE
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