Functionally fused antibodies--a novel adjuvant fusion system.
Antibodies capable of recognizing key molecular targets isolated e.g. by phage display technology have been used in the pursuit of new and improved therapies for prevalent human diseases. These approaches often take advantage of non-immunogenic antibody fragments to achieve specific toxin-, radioactivity- or effector-domain delivery. There is now a growing interest in using anti-idiotypic antibodies or other antigen mimics to induce potent immune responses against antigen structures in question. We have earlier reported on the functional rescue of antibodies that are active when fused to the phage, but inactive as soluble protein [Jensen, K.B., Larsen, M., Pedersen, J.S., Christensen, P.A., Alvarez-Vallina, L., Goletz, S., Clark, B.F. and Kristensen, P. (2002) Functional improvement of antibody fragments using a novel phage coat protein III fusion system. Biochem. Biophys. Res. Commun. 298, 566-73.]. The rescue was accomplished by maintaining the fusion between the antibody fragment and portions of the filamentous bacteriophage coat protein 3, as present in the original antibody-displaying phage. In the present study, we have applied this system in an attempt to improve immunogenicity of anti-idiotypic antibodies isolated by phage display. Here we demonstrate that by preserving linkage between phage antibody and the N-terminal domain of phage coat protein 3, we induce multimerization of the antibody fragments, and improve their immunogenicity. This immunization approach allows induction of anti-idiotypic antibodies in mice, and facilitates the use of antibodies that are non-functional as non-fused soluble protein.
Department of Molecular Biology, University of Aarhus, Denmark.
Martin
M
Larsen
Kim Bak
KB
Jensen
Peter Astrup
PA
Christensen
Eduardo
E
Suarez
Dominique
D
Paris
Laura
L
Sanz
Peter
P
Ravn
Delphine
D
Sauce
Philippe
P
Saas
Steffen
S
Goletz
Luis
L
Alvarez-Vallina
Peter
P
Kristensen
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins