2004
DOI: 10.1101/gr.2416604
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Abstract: Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a high-throughput cloning approach using the Gateway system to create a large set of expression clones encoding Plasmodium falciparum single-exon genes. Master clones and their ORFs were transferred en masse to multiple expression vectors. Target genes (n = 303) were selected using specific sets of criteria, including stage… Show more

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Cited by 58 publications
(54 citation statements)
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References 34 publications
(41 reference statements)
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“…Outstanding issues in malaria vaccine development Ab-mediated immunity Refs Identify mechanisms that maintain high titers of CS-protein-specific Abs for a prolonged period of time [33][34][35][36]66,67,69] Determine the role of Abs specific for non-CS-protein sporozoite Ags [16,73,74] Establish the contribution to protection of Ab responses targeting malaria proteins expressed on the surface of infected hepatocytes [75] Identify mechanisms to induce production of high-avidity Abs [38] T cell-mediated immunity Identify the key sporozoite and liver-stage Ags that stimulate protective CD4 and CD8 T cell-mediated immunity [23][24][25]64] Determine if there is a requirement for persisting CD4/CD8 T E cells or CD4/CD8 T CM cells (or both) for long-term protection [50,51,54,58,59,61,76] Establish whether there is a need for chronic stimulation from a persisting Ag depot to maintain long-lived intra-hepatic CD4/CD8 T E cells [36,49,60,61] Characterize the relative contribution of multi-functional CD4/CD8 T cells versus unifunctional CD4/CD8 T cells in conferring protection [27,41,42] Identify the primary site (liver or lymph node draining the liver) of pre-erythrocytic stage Ag-specific CD4/CD8 T cell activation [15,51,54,69] Determine whether CD4/CD8 T cells induced by subcutaneous or intramuscular immunization with subunit vaccines migrate to the liver [51] Identify a cross-presentation pathway that can be targeted by exogenous Ag to activate CD8 T cells ...…”
Section: Discussionmentioning
confidence: 99%
See 2 more Smart Citations
“…Outstanding issues in malaria vaccine development Ab-mediated immunity Refs Identify mechanisms that maintain high titers of CS-protein-specific Abs for a prolonged period of time [33][34][35][36]66,67,69] Determine the role of Abs specific for non-CS-protein sporozoite Ags [16,73,74] Establish the contribution to protection of Ab responses targeting malaria proteins expressed on the surface of infected hepatocytes [75] Identify mechanisms to induce production of high-avidity Abs [38] T cell-mediated immunity Identify the key sporozoite and liver-stage Ags that stimulate protective CD4 and CD8 T cell-mediated immunity [23][24][25]64] Determine if there is a requirement for persisting CD4/CD8 T E cells or CD4/CD8 T CM cells (or both) for long-term protection [50,51,54,58,59,61,76] Establish whether there is a need for chronic stimulation from a persisting Ag depot to maintain long-lived intra-hepatic CD4/CD8 T E cells [36,49,60,61] Characterize the relative contribution of multi-functional CD4/CD8 T cells versus unifunctional CD4/CD8 T cells in conferring protection [27,41,42] Identify the primary site (liver or lymph node draining the liver) of pre-erythrocytic stage Ag-specific CD4/CD8 T cell activation [15,51,54,69] Determine whether CD4/CD8 T cells induced by subcutaneous or intramuscular immunization with subunit vaccines migrate to the liver [51] Identify a cross-presentation pathway that can be targeted by exogenous Ag to activate CD8 T cells ...…”
Section: Discussionmentioning
confidence: 99%
“…Several CD4 and CD8 T cell epitopes have been mapped to the C terminus of the CS protein, and some of these are universal epitopes [19][20][21][22]. Currently, there are also extensive efforts to identify additional sporozoite proteins [23][24][25].…”
Section: The Rtss Human Protection Modelmentioning
confidence: 99%
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“…At the molecular level, the advances have been remarkable during this time and are set to continue with the genomic and proteomic data that are accumulating [23,24]. That said, the asexual-bloodstage target antigen that is undergoing the most intensive investigation is still, as in 1985, the merozoite surface protein MSP-1.…”
Section: Asexual-blood-stage Vaccinesmentioning
confidence: 99%
“…A fair conclusion that is drawn frequently from studies of natural immunity is that, for vaccine development, it would be better to focus on cryptic epitopes [24] rather than epitopes of the highly immunogenic polymorphic or clonally variant domains [29]. However, some promising liver-and blood-stage candidate vaccine molecules have been selected after analysis of naturally acquired immune responses [30,31].…”
Section: Asexual-blood-stage Vaccinesmentioning
confidence: 99%