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Peptide mimotopes of rabies virus glycoprotein with immunogenic activity.

Identifieur interne : 000734 ( PubMed/Curation ); précédent : 000733; suivant : 000735

Peptide mimotopes of rabies virus glycoprotein with immunogenic activity.

Auteurs : Mehdi Houimel [Tunisie] ; Koussay Dellagi

Source :

RBID : pubmed:19520204

Descripteurs français

English descriptors

Abstract

A random constrained hexapeptide phage display library (Cys-6aa-Cys) was screened with purified neutralizing human anti-rabies virus IgG antibodies (hRABVIgG) to identify peptides that correspond to or mimic natural epitopes on rabies virus glycoprotein (RABVG) and to investigate their immunogenicities in vivo. After four rounds of biopanning, 20 phage clones randomly selected for their specificity to hRABVIgG, effectively blocked the binding of the inactive rabies virus (RABV) to hRABVIgG. The phage clones were sequenced and the deduced amino acid sequences were derived (C-KRDSTW-C; C-KYLWSK-C; C-KYWLSR-C; C-KYWWSK-C; C-KYAWSR-C; C-KYSMSK-C). Alignments to the amino acid sequence of RABVG showed good match with the antigenic site III (at 330-338 aa), indicating that the hRABVIgG antibodies most likely recognize preferentially this antigenic site. The selected mimotopes were able to inhibit the interactions of the hRABVIgG antibodies with RABV in a dose-dependent manner. Subcutaneous administration of phageKRDSTW expressing the RABVG site III mimotope induced an RABVG-specific IgG response in BALB/c mice. The results indicated that peptide mimotopes when displayed on phages, are accessible to the mice immune system to trigger a humoral response and to induce IgG production. The RABVG site III mimotope (C-KRDSTW-C) would provide a new and promising concept for the development of rabies vaccine.

DOI: 10.1016/j.vaccine.2009.05.055
PubMed: 19520204

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pubmed:19520204

Le document en format XML

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<name sortKey="Houimel, Mehdi" sort="Houimel, Mehdi" uniqKey="Houimel M" first="Mehdi" last="Houimel">Mehdi Houimel</name>
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<nlm:affiliation>Laboratoire d'Immunopathologie Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia. mehdi.houimel@rns.tn</nlm:affiliation>
<country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Laboratoire d'Immunopathologie Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, Tunis-Belvédère</wicri:regionArea>
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<name sortKey="Dellagi, Koussay" sort="Dellagi, Koussay" uniqKey="Dellagi K" first="Koussay" last="Dellagi">Koussay Dellagi</name>
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<term>Animals (MeSH)</term>
<term>Antibodies, Viral (blood)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Antigens, Viral (immunology)</term>
<term>Epitopes (immunology)</term>
<term>Female (MeSH)</term>
<term>Glycoproteins (immunology)</term>
<term>Humans (MeSH)</term>
<term>Immunoglobulin G (blood)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred BALB C (MeSH)</term>
<term>Peptide Library (MeSH)</term>
<term>Rabies Vaccines (immunology)</term>
<term>Rabies virus (immunology)</term>
<term>Viral Envelope Proteins (immunology)</term>
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<term>Animaux (MeSH)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps antiviraux (sang)</term>
<term>Antigènes viraux (immunologie)</term>
<term>Banque de peptides (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Glycoprotéines (immunologie)</term>
<term>Humains (MeSH)</term>
<term>Immunoglobuline G (sang)</term>
<term>Mâle (MeSH)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée BALB C (MeSH)</term>
<term>Vaccins antirabiques (immunologie)</term>
<term>Virus de la rage (immunologie)</term>
<term>Épitopes (immunologie)</term>
</keywords>
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<term>Antibodies, Viral</term>
<term>Immunoglobulin G</term>
</keywords>
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<term>Antibodies, Viral</term>
<term>Antigens, Viral</term>
<term>Epitopes</term>
<term>Glycoproteins</term>
<term>Rabies Vaccines</term>
<term>Viral Envelope Proteins</term>
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<term>Anticorps antiviraux</term>
<term>Antigènes viraux</term>
<term>Glycoprotéines</term>
<term>Protéines de l'enveloppe virale</term>
<term>Vaccins antirabiques</term>
<term>Virus de la rage</term>
<term>Épitopes</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Rabies virus</term>
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<term>Anticorps antiviraux</term>
<term>Immunoglobuline G</term>
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<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
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<term>Banque de peptides</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
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<front>
<div type="abstract" xml:lang="en">A random constrained hexapeptide phage display library (Cys-6aa-Cys) was screened with purified neutralizing human anti-rabies virus IgG antibodies (hRABVIgG) to identify peptides that correspond to or mimic natural epitopes on rabies virus glycoprotein (RABVG) and to investigate their immunogenicities in vivo. After four rounds of biopanning, 20 phage clones randomly selected for their specificity to hRABVIgG, effectively blocked the binding of the inactive rabies virus (RABV) to hRABVIgG. The phage clones were sequenced and the deduced amino acid sequences were derived (C-KRDSTW-C; C-KYLWSK-C; C-KYWLSR-C; C-KYWWSK-C; C-KYAWSR-C; C-KYSMSK-C). Alignments to the amino acid sequence of RABVG showed good match with the antigenic site III (at 330-338 aa), indicating that the hRABVIgG antibodies most likely recognize preferentially this antigenic site. The selected mimotopes were able to inhibit the interactions of the hRABVIgG antibodies with RABV in a dose-dependent manner. Subcutaneous administration of phageKRDSTW expressing the RABVG site III mimotope induced an RABVG-specific IgG response in BALB/c mice. The results indicated that peptide mimotopes when displayed on phages, are accessible to the mice immune system to trigger a humoral response and to induce IgG production. The RABVG site III mimotope (C-KRDSTW-C) would provide a new and promising concept for the development of rabies vaccine.</div>
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