CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies |
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Authors: | Chie Hashimoto Wataru Nomura Tetsuo Narumi Masayuki Fujino Toru Nakahara Naoki Yamamoto Tsutomu Murakami Hirokazu Tamamura |
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Institution: | 1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan;2. AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore |
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Abstract: | Despite almost 30 years since the identification of the human immunodeficiency virus type I (HIV-1), development of effective AIDS vaccines has been hindered by the high mutability of HIV-1. The HIV-1 co-receptors CCR5 and CXCR4 are genetically stable, but viral proteins may mutate rapidly during the course of infection. CXCR4 is a seven transmembrane G protein-coupled receptor, possessing an N-terminal region (NT) and three extracellular loops (ECL1-3). Previous studies have shown that the CXCR4-ED-derived peptides inhibit the entry of HIV-1 by interacting with gp120, an HIV-1 envelope glycoprotein. In the present study, antigenicity of CXCR4-derived peptides has been investigated and the anti-HIV-1 effects of induced antisera have been assessed. It was found that CXCR4-ED-derived antigen molecules immunize mice, showing that the linear peptides have higher antigenicity than the cyclic peptides. The L1- and L2-induced antisera inhibited the HIV-1 entry significantly, while anti-N1 antibodies have no inhibitory activity. This study produced promising examples for the design of AIDS vaccines which target the human protein and can overcome mutability of HIV-1. |
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Keywords: | HIV-1 co-receptor CXCR4 Extracellular domain AIDS vaccine Multi-antigen peptide |
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