Scientific Tracks Abstracts: JAA
Using in vitro selections via phage display from both a human universal library or from libraries generated aft er immunisation, we were able to isolate a panel of recombinant antibodies to various viruses considered to be a bioterrorist threat agent. In particular, antibodies to Venezuelan equine encephalitis virus (VEEV), infl uenza H5N1, western equine encephalitis virus (WEEV), as well as other bioterrorist threat reagents like anthrax and ricin, were succesfully generated. A major advantage of in vitro antibody selection is the ability to carefully control the biochemical conditions during the very moment of selection, for example, by presentation of specifi c conformations of the target antigen, or by including competitors to direct selection towards specifi c targets or epitopes of interest. Sequential use of diff erent antigens facilitates the selection of shared epitopes. Here, we describe several cases where these strategies were crucial for the selection of novel antibodies with enhanced properties. Th e identifi cation of specifi c human antibodies to VEEV benefi ted from the possibility to add soluble competitors during the in vitro selection process. In particular, the addition of host cell extract allowed to select for epitopes specifi c for the virus even allowing to use a virus preparation containing a substantial fraction of host cell proteins. In case of the neutralizing antibodies to a novel epitope in infl uenza (bird fl u), a very broad specifi city range was obtained by a sequential panning strategy on evolutionary distant virus strains, to identify the common epitope. Th ese examples illustrate in vitro selection strategies which are be broadly applicable to other problems in virology.
Stefan Dübel is Full Professor of Biotechnology and Director of the Biotechnology department. He pioneered in vitro antibody selection technologies, resulting in several key inventions including antibody phage display (e.g. US-Patent 5849500) and human antibody libraries with randomised CDRs (e.g. US-Patent 5840479). His lab continued to contribute to multiple topics related to human antibody engineering and phage display, e.g. Hyperphage technology (2001) or targeted human RNases for cancer therapy (2008). He is initiator of the ?Antibody factory? of the German National Gemome Research Network and editor of the three volume ?Handbook of Therapeutic Antibodies? and other antibody engineering books.