2007 Fiscal Year Final Research Report Summary
Production of human monoclonal antibodies, which inhibit in vitro growth of Plasmodium falciparum
| Project/Area Number |
18590407
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Tokai University |
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Principal Investigator |
TACHIBANA Hiroshi Tokai University, School of Medicine, Associate Professor (10147168)
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| Project Period (FY) |
2006 – 2007
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| Keywords | malaria / Plasmodium falciparum / human monoclonal antibod / Fab / merozoite surface protein 1 |
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| Research Abstract |
An effective vaccine for malaria has not yet been developed. Passive immunotherapy with human monoclonal antibodies may provide a valuable therapeutic alternative. A combinatorial immunoglobulin gene library was constructed from lymphocytes of patients infected with Plasmodium falciparum and screened for the production of human monoclonal antibodies to the C terminal 19-kDa fragment of P. falciparum merozoite surface protein 1 (MSP-1_<19>). MSP-lis-specific Fab fragments were produced in bacterial expression system. Immunofluorescence staining of P. falciparum merozoites by the Fab fragments was demonstrated on FCR3 and 3D7 strains, which were representatives of dimorphic allelic variants in MSP-1_<19>, suggesting the Fab's reativity to a conserved region. To examine whether the epitope for these Fabs was recognized by immune sera, competition ELISA was also performed using sera from ten malaria-immune individuals in the Solomon Islands or plasmas from eight donors of lymphocytes. Three of the immune sera and three of donors' plasmas showed significant inhibition compared with control sera. The effect of single amino acid modifications in the third complementarity-determining regions of the heavy and light chains on affinity was examined in one of the Fab fragments, P125. Recombination PCR was used to modify Tyr^<92> or Ile^<97> in the light chain and Val^<101> or Trp^<107> in the heavy chain. No effective replacements for Tyr^<92> and Val^<101> were found, but possible substitutions of 11e^<97> with Gly, Leu, Glu, Ala and Ser, and of Trp^<107>with Arg and Ser were demonstrated. Of these modified Fab fragments, the affinities of Fabs with Ile^<97>Leu and Typ^<107>Ser mutations were slightly higher than that of the original Fab. The modified antibodies may be applicable to analyze epitope structures of MSP-1_<19>.
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Research Products
(14 results)
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[Journal Article] Modification of a human monoclonal antibody Fab fragment specific for Plasmodium falciparum 19-kilodalton C-terminal merozoite surface protein 1 by site-directed mutagenesis2008
Author(s)
Y.-L., Tao, X.-J., Cheng, Y.-F., Fu, H., Tsukamoto, E., Yoshihara, H., Tachibana
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Journal Title
Parasitol. Res 103(in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Production of high-affinity human monoclonal antibody Fab fragments to the 19-kilodalton C-terminal merozoite surface protein 1 of Plasmodium falciparum2007
Author(s)
X.-J., Cheng, H., Hayasaka, K., Watanabe, Y.-L., Tao, J.-Y., Liu, H., Tsukamoto, T., Horii, K., Tanabe, H., Tachibana
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Journal Title
Infect. Immun 75(7)
Pages: 3614-3620
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] An Entamoeba sp. strain isolated from rhesus monkey is virulent but genetically different from Entamoeba histolytica2007
Author(s)
H., Tachibana, T., Yanagi, K., Pandey, X.-J., Cheng, S., Kobayashi, J. B., Sherchand, H., Kanbara
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Journal Title
Mol. Biochem. Parasitol 153(2)
Pages: 107-114
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Primary structure, expression and localization of two intermediate subunit lectins of Entamoeba dispar that contain multiple CXXC motifs2007
Author(s)
H., Tachibana, X.-J., Cheng, S., Kobayashi, Y., Okada, J., Itoh, T., Takeuchi
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Journal Title
Parasitology 134(14)
Pages: 1989-1999
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Production of an anti-severe acute respiratory syndrome(SARS) coronavirus human monoclonal antibody Fab fragment by using a combinatorial immunoglobulin gene library derived from patients who recovered from SARS2006
Author(s)
J., Liu, H., Shao, Y., Tao, B., Yang, L., Qian, X., Yang, B., Cao, G., Hu, H., Tachibana, X., Cheng
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Journal Title
Clin. Vaccine Immunol 13(5)
Pages: 594-597
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Production and modification of human monoclonal antibody Fab fragments to the 19-kilodalton C-terminal merozoite surface protein 1 of Plasmodium falciparum.2008
Author(s)
H., Tachibana, X.-J., Cheng, Y.-L., Tao, Y.-F., Fu, E., Yoshihara, K., Tanabe
Organizer
13th International Congress on Infectious Diseases
Place of Presentation
Kuala Lumpur
Year and Date
2008-06-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Bacterial expression of human monoclonal antibody Fab fragments recognizing merozoite surface protein-1ts of Plasmodium falciparum.2006
Author(s)
X., Cheng, H., Hayasaka, K., Watanabe, Y., Tao, J., Liu, K., Tanabe, H., Tachibana
Organizer
The 75th Annual Meeting of the Japanese Society of Parasitology
Place of Presentation
Hirosaki
Year and Date
2006-05-20
Description
「研究成果報告書概要(欧文)」より
