Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets
| Autor: | Ellen J. Collarini, Shelley Izquierdo, Yasmina Noubia Abdiche, Darlene Pedersen, Rian Harriman, Daniel Bedinger, Kathryn H. Ching, Philip A. Leighton, Harriman William Don, Robert J. Etches, Marie-Cecile van de Lavoir, Lei Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class Transgene T-Lymphocytes Immunology Antibody Affinity Immunoglobulins Biology Monoclonal antibody Immunoglobulin light chain Antibodies Monoclonal Humanized Epitope transgenic chicken Animals Genetically Modified 03 medical and health sciences Epitopes Immune system Species Specificity Antibody Specificity Report medicine Immunology and Allergy Animals Humans Antigens B cell epitope B-Lymphocytes Linear epitope Virology Molecular biology conserved target binning 030104 developmental biology medicine.anatomical_structure biology.protein Immunization Antibody human antibody Chickens Epitope Mapping |
| Zdroj: | mAbs |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | Transgenic animal platforms for the discovery of human monoclonal antibodies have been developed in mice, rats, rabbits and cows. The immune response to human proteins is limited in these animals by their tolerance to mammalian-conserved epitopes. To expand the range of epitopes that are accessible, we have chosen an animal host that is less phylogenetically related to humans. Specifically, we generated transgenic chickens expressing antibodies from immunoglobulin heavy and light chain loci containing human variable regions and chicken constant regions. From these birds, paired human light and heavy chain variable regions are recovered and cloned as fully human recombinant antibodies. The human antibody-expressing chickens exhibit normal B cell development and raise immune responses to conserved human proteins that are not immunogenic in mice. Fully human monoclonal antibodies can be recovered with sub-nanomolar affinities. Binning data of antibodies to a human protein show epitope coverage similar to wild type chickens, which we previously showed is broader than that produced from rodent immunizations. |
| Databáze: | OpenAIRE |
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