Successful mimicry of a complex viral antigen by multiple peptide insertions in a carrier protein.
The antigenic properties of a viral peptide from the surface of foot-and-mouth disease virus particles have been successfully mimicked by multiple insertion in solvent-exposed regions of Escherichia coli beta-galactosidase. By increasing the number of viral peptides per enzyme monomer, the average IC(50) of hybrid proteins in a competitive enzyme-linked immunosorbent assay) have decreased to values close to that presented by natural virions. Moreover, the antigenic diversity of these new recombinant enzymes when measured with different anti-virus antibodies has also been largely reduced, indicating a better presentation of the epitopes located in the viral peptide. Although bivalent antibody binding could have been favoured by multiple presentation, conformational modifications of the viral peptide, due to the presence of other insertions or a cooperative antibody binding cannot be excluded. In addition, a multidimensional antigenic analysis have grouped together the multiple-inserted proteins with the native virus, suggesting that increasing the number of insertions could be a good strategy to reproduce the antigenic properties of an immunoreactive peptide in a natural multimeric disposition.
Feliu
J X
JX
Institut de Biologia Fonamental and Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Belllaterra, 08193, Barcelona, Spain. jxfeliu@einstein.uab.es
Carbonell
X
X
Villaverde
A
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D005537:Aphthovirus / Q000276:immunology*; D002213:Capsid / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D036022:Capsid Proteins; D004355:Drug Stability; D004926:Escherichia coli; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D001616:beta-Galactosidase / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase