This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Misumi, S.
Right arrow Articles by Shoji, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Misumi, S.
Right arrow Articles by Shoji, S.

 Previous Article  |  Next Article 

Journal of Virology, December 2001, p. 11614-11620, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11614-11620.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A Cyclic Dodecapeptide-Multiple-Antigen Peptide Conjugate from the Undecapeptidyl Arch (from Arg168 to Cys178) of Extracellular Loop 2 in CCR5 as a Novel Human Immunodeficiency Virus Type 1 Vaccine

Shogo Misumi, Reina Nakajima, Nobutoki Takamune, and Shozo Shoji*

Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan

Received 4 June 2001/Accepted 18 August 2001

A cyclic closed-chain dodecapeptide (cDDR5) mimicking the conformation-specific domain of CCR5 was prepared in which Gly-Asp, as a dipeptide forming a spacer arm, links the amino and carboxyl termini of the decapeptidyl linear chain (Arg168 to Thr177) derived from the undecapeptidyl arch (UPA; Arg168 to Cys178) of extracellular loop 2 (ECL2) in CCR5. Novel monoclonal antibodies were raised against cDDR5 conjugated with a multiple-antigen peptide (cDDR5-MAP), and the purified antibody [KB8C12, immunoglobulin M(kappa )] reacted with cDDR5, but not with linear DDR5, in real-time biomolecular interaction analysis using surface plasmon resonance. The antibody also reacted with cells expressing CCR5, but not with cells expressing CXCR4, and the immunoreaction was competed by cDDR5-MAP. The antibody significantly interfered with chemotaxis induced by macrophage inflammatory protein, 1beta , and at a concentration of 1.67 nM it almost completely inhibited infection by human immunodeficiency virus type 1 (HIV-1) R5, but not by HIV-1 X4, as observed by use of a new phenotypic assay for drug susceptibility of HIV-1 using the CCR5-expressing HeLa CD4+ cell clone 1-10 (MAGIC-5). Furthermore, cDDR5-MAP suppressed infection by HIV-1 R5 at relatively high concentrations (50 to 400 µM) in a dose-dependent manner but did not suppress infection by HIV-1 X4. Taken together, these results indicate that the antibody is conformation specific and recognizes the conformation-specific domain of the UPA of ECL2. Moreover, both the antibody and its immunogen, the cDDR5-MAP conjugate, may be useful in developing a new candidate vaccine for HIV therapy.

* Corresponding author. Mailing address: Kumamoto University, Department of Biochemistry, Faculty of Pharmaceutical Sciences, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan. Phone: 81-96-371-4362. Fax: 81-96-362-7800. E-mail: shoji{at}gpo.kumamoto-u.ac.jp.

Journal of Virology, December 2001, p. 11614-11620, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11614-11620.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Misumi, S., Masuyama, M., Takamune, N., Nakayama, D., Mitsumata, R., Matsumoto, H., Urata, N., Takahashi, Y., Muneoka, A., Sukamoto, T., Fukuzaki, K., Shoji, S. (2009). Targeted Delivery of Immunogen to Primate M Cells with Tetragalloyl Lysine Dendrimer. J. Immunol. 182: 6061-6070 [Abstract] [Full Text]  
  • Misumi, S., Nakayama, D., Kusaba, M., Iiboshi, T., Mukai, R., Tachibana, K., Nakasone, T., Umeda, M., Shibata, H., Endo, M., Takamune, N., Shoji, S. (2006). Effects of Immunization with CCR5-Based Cycloimmunogen on Simian/HIVSF162P3 Challenge. J. Immunol. 176: 463-471 [Abstract] [Full Text]  
  • Nakayama, D., Misumi, S., Mukai, R., Tachibana, K., Umeda, M., Shibata, H., Takamune, N., Shoji, S. (2005). Suppression of Multiclade R5 and X4 Human Immunodeficiency Virus Type-1 Infections by a Coreceptor-Based Anti-HIV Strategy. J Biochem 138: 571-582 [Abstract] [Full Text]  
  • Agrawal, L., VanHorn-Ali, Z., Berger, E. A., Alkhatib, G. (2004). Specific inhibition of HIV-1 coreceptor activity by synthetic peptides corresponding to the predicted extracellular loops of CCR5. Blood 103: 1211-1217 [Abstract] [Full Text]  
  • Misumi, S., Endo, M., Mukai, R., Tachibana, K., Umeda, M., Honda, T., Takamune, N., Shoji, S. (2003). A Novel Cyclic Peptide Immunization Strategy for Preventing HIV-1/AIDS Infection and Progression. J. Biol. Chem. 278: 32335-32343 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»