Antigen Discovery

Vaccinex has a wealth of information and experience creating recombinant vaccinia virus with any cDNAs. We use this technology primarily as a discovery platform for antibody therapeutics, but have also developed an innovative approach for identification of new target antigens.

Antigen discovery in this context begins with a molecule that has interesting binding properties. This can be a phage or yeast displayed single chain Fv, it can be a peptide either presented on phage or directly conjugated with a tag, or it can be an antibody generated against whole cells. In all cases, these binding molecules are identified through a panning experiment or through a functional screen wherein there is demonstrated binding to a cell line or tissue of interest, but not to a control (for example, a panning experiment designed to identify antibodies that bind to tumor cells but not normal cells).

We use the antigen-positive tissue or cell line of interest to isolate cDNAs and create a recombinant library in vaccinia virus. We then infect antigen-negative cells at a multiplicity of infection (MOI) of 1 and incubate the infected cells with the binding molecule engineered, either directly or indirectly with a fluorescent marker. Fluorescence-activated cell sorting (FACS) can then be employed to isolate cells that are positive for the target. Virus is harvested from these cells and can be used in subsequent rounds of infection and selection to take full advantage of the reiterative nature of our technology and ensure that even low frequency events are captured.

In 2009 Vaccinex successfully completed an antigen discovery project with Bayer Schering AG whereby a significant number of novel binding molecules with interesting binding properties were screened using our recombinant cDNA libraries in order to find the antigen. The result was 100% success in identifying the antigen for all binding molecules supplied.