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

The highly conserved amino acid sequence ELDKWA of HIV-1 gp41 has been inse rted into Escherichia coli MalE protein which had been shown to be an adequ ate carrier to present foreign epitopes to the immune system. We first inve stigated whether eight different permissive sites of MalE are able to toler ate an insertion of 7-50 residues encoding this epitope. Secondly, antigeni city:of the epitope inserted in MalE protein was estimated from monoclonal antibody 2F5 binding analysis using the BIAcore(R) technology and its immun ogenicity 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 epitop e and its immunogenicity. Increasing the length of the inserted epitope, as well as inserting multicopies of this epitope increased both its antigenic ity and immunogenicity. However, none of the MalE hybrid proteins tested in duced 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 Scienc e Ltd. All rights reserved.