Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the MalE protein

被引:113
作者
Coëffier, E
Clément, JM
Cussac, V
Khodaei-Boorane, N
Jehanno, M
Rojas, M
Dridi, A
Latour, M
El Habib, R
Barré-Sinoussi, F
Hofnung, M
Leclerc, C
机构
[1] Inst Pasteur, Unite Biol Regulat Immunitaires, F-75724 Paris 15, France
[2] Inst Pasteur, CNRS, UA 1444, Unite Programmat Mol & Toxicol Genet, Paris, France
[3] Aventis Pasteur, Marcy Etoile, France
[4] Inst Pasteur, Unite Biol Retrovirus, Paris, France
关键词
HIV-1; gp41; epitope; MalE protein;
D O I
10.1016/S0264-410X(00)00267-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The highly conserved amino acid sequence ELDKWA of HIV-1 gp41 has been inserted into Escherichia coli MalE protein which had been shown to be an adequate carrier to present foreign epitopes to the immune system. We first investigated whether eight different permissive sites of MalE are able to tolerate an insertion of 7-50 residues encoding this epitope. Secondly, antigenicity:of the epitope inserted in MalE protein was estimated from monoclonal antibody 2F5 binding analysis using the BIAcore(R) technology and its immunogenicity in mice was measured as the ability of hybrid proteins to elicit antibodies against a synthetic peptide containing this epitope. This study revealed a good correlation between the antigenicity of the inserted epitope and its immunogenicity. Increasing the length of the inserted epitope, as well as inserting multicopies of this epitope increased both its antigenicity and immunogenicity. However, none of the MalE hybrid proteins tested induced anti-HIV-1 neutralizing antibodies. This study strongly suggests that the capacity of the 2F5 epitope to induce neutralizing antibodies depends on the molecular context in which it is presented. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:684 / 693
页数:10
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