title: CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies.
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.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.forename: Wataru
authors.initials: W
authors.lastname: Nomura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.forename: Toru
authors.initials: T
authors.lastname: Nakahara
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Murakami
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D015483:HIV Antibodies / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D015483:HIV Antibodies; D016655:HIV Core Protein p24; D010455:Peptides; D019718:Receptors, CXCR4; C514799:p24 protein, Human Immunodeficiency Virus Type 1
keywords: AIDS vaccine; CXCR4; Extracellular domain; HIV-1 co-receptor; Multi-antigen peptide