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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-5-6
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pubmed:databankReference |
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pubmed:abstractText |
A Plasmodium falciparum chimeric protein 2.9 (PfCP-2.9) was constructed consisting of the C-terminal regions of two leading malaria vaccine candidates, domain III of apical membrane ag-1 (AMA-1) and 19-kDa C-terminal fragment of the merozoite surface protein 1 (MSP1). The PfCP-2.9 was produced by Pichia pastoris in secreted form with a yield of 2600 mg/L and approximately 1 g/L of final product was obtained from a three-step purification process. Analysis of conformational properties of the chimeric protein showed that all six conformational mAbs interacted with the recombinant protein were reduction-sensitive, indicating that fusion of the two cysteine-rich proteins retains critical conformational epitopes. PfCP-2.9 was found to be highly immunogenic in rabbits as well as in rhesus monkeys (Macaca mulatta). The chimeric protein induced both anti-MSP1-19 and anti-AMA-1(III) Abs at levels 11- and 18-fold higher, respectively, than individual components did. Anti-PfCP-2.9 sera from both rabbits and rhesus monkeys almost completely inhibited in vitro growth of the P. falciparum FCC1/HN and 3D7 lines when tested at a 6.7-fold dilution. It was shown that the inhibition is dependent on the presence of Abs to the chimeric protein and their disulfide bond-dependent conformations. Moreover, the activity was mediated by a combination of growth-inhibitory Abs generated by the individual MSP1-19 and AMA-1(III) of PfCP-2.9. The combination of the extremely high yield of the protein and enhancement of its immune response provides a basis to develop an effective and affordable malaria vaccine.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Protozoan,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Protozoan,
http://linkedlifedata.com/resource/pubmed/chemical/Antiprotozoal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Malaria Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PfCPK protein, Plasmodium falciparum,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protozoan Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Subtilisins,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA,
http://linkedlifedata.com/resource/pubmed/chemical/apical membrane antigen I...,
http://linkedlifedata.com/resource/pubmed/chemical/sub-2 protein, Plasmodium falciparum
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
172
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6167-74
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15128804-Adjuvants, Immunologic,
pubmed-meshheading:15128804-Animals,
pubmed-meshheading:15128804-Antibodies, Protozoan,
pubmed-meshheading:15128804-Antigens, Protozoan,
pubmed-meshheading:15128804-Antiprotozoal Agents,
pubmed-meshheading:15128804-Calcium-Binding Proteins,
pubmed-meshheading:15128804-Growth Inhibitors,
pubmed-meshheading:15128804-Macaca mulatta,
pubmed-meshheading:15128804-Malaria Vaccines,
pubmed-meshheading:15128804-Membrane Proteins,
pubmed-meshheading:15128804-Molecular Sequence Data,
pubmed-meshheading:15128804-Plasmodium falciparum,
pubmed-meshheading:15128804-Protein Kinases,
pubmed-meshheading:15128804-Protozoan Proteins,
pubmed-meshheading:15128804-Rabbits,
pubmed-meshheading:15128804-Recombinant Fusion Proteins,
pubmed-meshheading:15128804-Subtilisins,
pubmed-meshheading:15128804-Vaccines, DNA
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pubmed:year |
2004
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pubmed:articleTitle |
Fusion of two malaria vaccine candidate antigens enhances product yield, immunogenicity, and antibody-mediated inhibition of parasite growth in vitro.
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pubmed:affiliation |
Department of Etiologic Biology, Second Military Medical University, Shanghai, China. malaria@guomai.sh.cn
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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