Functionally fused antibodies--a novel adjuvant fusion system

TY - JOUR

T1 - Functionally fused antibodies--a novel adjuvant fusion system

AU - Larsen, Martin

AU - Jensen, Kim Bak

AU - Christensen, Peter Astrup

AU - Suarez, Eduardo

AU - Paris, Dominique

AU - Sanz, Laura

AU - Ravn, Peter

AU - Sauce, Delphine

AU - Saas, Philippe

AU - Goletz, Steffen

AU - Alvarez-Vallina, Luis

AU - Kristensen, Peter

PY - 2008/12/31

Y1 - 2008/12/31

N2 - 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.

AB - 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.

KW - Adjuvants, Immunologic/genetics

KW - Animals

KW - Antibodies, Anti-Idiotypic/immunology

KW - Antibodies, Monoclonal/genetics

KW - Capsid Proteins/genetics

KW - Female

KW - Humans

KW - Mice

KW - Mice, Inbred BALB C

KW - Recombinant Fusion Proteins/genetics

U2 - 10.1016/j.jim.2008.09.015

DO - 10.1016/j.jim.2008.09.015

M3 - Journal article

C2 - 18854189

SN - 0022-1759

VL - 339

SP - 220

EP - 227

JO - Journal of Immunological Methods

JF - Journal of Immunological Methods

IS - 2

ER -