Development of HIV-1 coreceptor-based HIV /AIDS defense vaccine

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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.