Suppression of multiclade R5 and X4 human immunodeficiency virus type-1 infections by a coreceptor-based anti-HIV strategy.

Abstract

A cyclic chimeric dodecapeptide (cCD) mimicking the conformation-specific domains of CCR5 and CXCR4 was prepared in which Gly-Asp links the amino and carboxyl termini of two combined pentapeptides (S169-G173 of CCR5; E179-R183 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 -VI were effective against only R5 laboratory strains, and also against some X4 and R5 primary isolates. CPMAb-IV and -V had potent antiviral activities against the R5 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-MAP is a candidate multiclade immunogen that can be used to block multiclade R5 and X4 HIV-1 infections.

• Authors: Daisuke Nakayama, Shogo Misumi, Ryouzaburo Mukai, Kuniomi Tachibana, Mamoru Umeda, Hideaki Shibata, Nobutoki Takamune, Shozo Shoji
• Journal: Journal of biochemistry (J Biochem) Vol. 138 Issue 5 Pg. 571-82 (Nov 2005) ISSN: 0021-924X [Print] England
• PMID: 16272569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• Antibodies, Monoclonal
• Peptides
• Peptides, Cyclic
• Receptors, CCR5
• Receptors, CXCR4
• cyclic chimeric dodecapeptidyl multiple antigen peptide

Topics

• AIDS Vaccines
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Disease Progression
• HIV Infections (drug therapy)
• HIV-1 (immunology)
• Humans
• Macaca fascicularis
• Mice
• Mice, Inbred BALB C
• Peptides (immunology, metabolism)
• Peptides, Cyclic
• Protein Conformation
• Receptors, CCR5 (chemistry, immunology)
• Receptors, CXCR4 (chemistry, immunology)
• Simian Immunodeficiency Virus (immunology)