title: Genetic engineering of attenuated malaria parasites for vaccination.
abstract: Vaccination with live-attenuated Plasmodium sporozoites that arrest in the liver can completely protect against a malaria infection both in animal models and in humans; this has provided the conceptual basis for the most promising, but also challenging, approach to develop an efficacious malaria vaccine. Advances in genetic manipulation of Plasmodium in conjunction with improved genomic and biological information has enabled new approaches to design genetically attenuated parasites (GAPs). In this review we discuss the principles in discovery and development of GAPs in preclinical models that are important in selecting GAP parasites for first-in-human clinical studies. Finally, we highlight the challenges in manufacture, formulation and delivery of a live-attenuated whole parasite malaria vaccine, as well as the further refinements that may be implemented in the next generation GAP vaccines.
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. S.M.Khan@lumc.nl
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mikolajczak
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005818:Genetic Engineering; D006801:Humans; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology*; D010961:Plasmodium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000235:genetics* / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines; D014613:Vaccines, Attenuated