| Project/Area Number |
16390023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
SHOJI Shozo Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 教授 (60040317)
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| Co-Investigator(Kenkyū-buntansha) |
MISUMI Shogo Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 助教授 (40264311)
TAKAMUNE Nobutoki Kumamoto University, Faculty of Medical and Pharmaceutical Science, Ph.D., Professor, 大学院医学薬学研究部, 助手 (60322749)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | HIV-1 / Vaccine / Coreceptor / UPA |
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| Research Abstract |
A cyclic chimeric dodecapeptide (cCD) mimicking the conformation-specific domains of CCR5 and CXCR4 was prepared in which Gly-Asplinkstheaminoandcarboxylterminioftwocombinedpentapeptides(S_<169>-G_<173> of CCR5 ; E_<179>-R_<183> of CXCR4) derived from human immunodeficiency virus type-1 (HIV-1) coreceptors. The immunization of Balb/c mice with cCD conjugated with a multiple-antigen peptide (cCD-MAP) induced seven cCD-specific monoclonal antibodies (mAbs, CPMAb-I to-VII) that reacted with native CCR5 and CXCR4. Among the tested mAbs, CPMAb-I and-II potently inhibited the infection of both the R5 and X4 laboratory strains. CPMAb-III and-V1wereeffectiveagainstonlyR5laboratorystrains, and also against some X4 and R5 primary isolates. CPMAb-IV and-Vhadpotent antiviral activities againsttheR5 and X4 primary isolates. In particular, CPMAb-VII was protective against not only R5 and X4 laboratory strains, but also most of the R5 and X4 primary isolates. Moreover, cCD-MAP immunization also induced antibodies that were effective against R5 and X4 multiclade HIV-1 isolates in vitro in two of three cynomolgus monkeys. Taken together, the results suggest that cCD-MAPisacandidatemulticladeimmunogenthatcanbeused to block multiclade R5 and X4 HIV-1 infections.
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