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 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.
Coëffier
E
E
Unité de Biologie des Régulations Immunitaires, Institut Pasteur 25, rue du Docteur Roux, 75724, Cedex 15, Paris, France.
Clément
J M
JM
Cussac
V
V
Khodaei-Boorane
N
N
Jehanno
M
M
Rojas
M
M
Dridi
A
A
Latour
M
M
El Habib
R
R
Barré-Sinoussi
F
F
Hofnung
M
M
Leclerc
C
C
D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D007114:Immunization; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D009500:Neutralization Tests; D033902:Periplasmic Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D029968:Escherichia coli Proteins; D015700:HIV Envelope Protein gp41; C461619:MalE protein, E coli; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; D011994:Recombinant Proteins; C461599:maltose transport system, E coli