Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated "Human Immune System'' Mice
Pablo D Becker, Nicolas Legrand, Caroline MM van Geelen, Miriam Noerder, Nicholas D Huntington, Annick Lim, Etsuko Yasuda, Sean A Diehl, Ferenc A Scheeren, Michael Ott, Kees Weijer, Heiner Wedemeyer, James P Di Santo, Tim Beaumont, Carlos A Guzman, Hergen Spits
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2010
BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the 'humanization' of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization ..View full abstract
Awarded by National Institutes of Health (NIH-NIAID)
Awarded by German Research Foundation
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This work was supported by grants from the Bill and Melinda Gates Foundation "Grand Challenges in Global Health'' Program (GC4 - "Human Vaccine Consortium''; http://www.hv-consortium.org/), the Wijnand M. Pon Foundation, College de France, Fondation pour la Recherche Medicale (FRM), Institut Pasteur and the Institut National de la Sante et de la Recherche Medicale (INSERM). N.D.H. was supported by the Human Frontiers Science Program. S.A.D. was supported by the National Institutes of Health (NIH-NIAID grant # F32 AI063846). C.A. G. was supported by a grant from the Excellence Cluster "From Regenerative Biology to reconstructive Therapy'' by the German Research Foundation (EXC 62/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was also in part financially supported by AIMM Therapeutic who did have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.