Generation of Stable Eukaryotic Cell Lines Expressing High Yields of Therapeutic Human Antibodies Against Biowarfare Viral Threat Agents

The proposed effort aims to test the protective efficacy of full length VACV-specific human mAbs derived from a phage FAb combinatorial library in a series of relevant in vitro and in vivo studies. To date, two such mAbs have been partially characterized and shown to neutralize VACV replication in vitro. FAbs to additional VACV targets known to elicit protective immunity in vivo are being identified and converted to full length IgGs. The ultimate goal of this effort is to generate a combinational therapeutic of human mAbs to several neutralizing VACV proteins, that confer the highest degree of protection against vaccinia, smallpox, monkeypox, and other orthopoxvirus infections. This approach is based on previous work showing that protective immunity to orthopoxviruses is best achieved when multiple neutralizing epitopes are targeted (Hooper et al., 2000, Hooper et al., 2003, Hooper et al., 2004, Chen et al., 2006)