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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-23
pubmed:abstractText
We describe a novel approach for identifying target antigens for preerythrocytic malaria vaccines. Our strategy is to rapidly test hundreds of DNA vaccines encoding exons from the Plasmodium yoelii yoelii genomic sequence. In this antigen identification method, we measure reduction in parasite burden in the liver after sporozoite challenge in mice. Orthologs of protective P. y. yoelii genes can then be identified in the genomic databases of Plasmodium falciparum and Plasmodium vivax and investigated as candidate antigens for a human vaccine. A pilot study to develop the antigen identification method approach used 192 P. y. yoelii exons from genes expressed during the sporozoite stage of the life cycle. A total of 182 (94%) exons were successfully cloned into a DNA immunization vector with the Gateway cloning technology. To assess immunization strategies, mice were vaccinated with 19 of the new DNA plasmids in addition to the well-characterized protective plasmid encoding P. y. yoelii circumsporozoite protein. Single plasmid immunization by gene gun identified a novel vaccine target antigen which decreased liver parasite burden by 95% and which has orthologs in P. vivax and P. knowlesi but not P. falciparum. Intramuscular injection of DNA plasmids produced a different pattern of protective responses from those seen with gene gun immunization. Intramuscular immunization with plasmid pools could reduce liver parasite burden in mice despite the fact that none of the plasmids was protective when given individually. We conclude that high-throughput cloning of exons into DNA vaccines and their screening is feasible and can rapidly identify new malaria vaccine candidate antigens.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-10775787, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-10866209, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-10903750, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-10992502, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11075367, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11076863, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11181995, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11231557, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11256614, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11493695, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11738713, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11854091, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11880620, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-11932250, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-12364791, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-12368864, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-12368865, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-12368866, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-12368870, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-15275087, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-1988490, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-7566175, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-7937907, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-8628694, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-8666931, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-9234529, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-9381177, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-9550412, http://linkedlifedata.com/resource/pubmed/commentcorrection/14977966-9804551
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0019-9567
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1594-602
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:14977966-Humans, pubmed-meshheading:14977966-Animals, pubmed-meshheading:14977966-Mice, pubmed-meshheading:14977966-Malaria, pubmed-meshheading:14977966-Liver, pubmed-meshheading:14977966-Injections, Intramuscular, pubmed-meshheading:14977966-Female, pubmed-meshheading:14977966-Base Sequence, pubmed-meshheading:14977966-Mice, Inbred BALB C, pubmed-meshheading:14977966-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:14977966-Antibodies, Protozoan, pubmed-meshheading:14977966-Cloning, Molecular, pubmed-meshheading:14977966-Plasmids, pubmed-meshheading:14977966-DNA, Protozoan, pubmed-meshheading:14977966-Genome, Protozoan, pubmed-meshheading:14977966-Antigens, Protozoan, pubmed-meshheading:14977966-Exons, pubmed-meshheading:14977966-DNA Primers, pubmed-meshheading:14977966-Plasmodium yoelii, pubmed-meshheading:14977966-Polymerase Chain Reaction
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