Identification of a strongly activating human anti-CD40 antibody that suppresses HIV type 1 infection.

We characterized the functional properties of a novel set of human anti-CD40 monoclonal antibodies originating from a human phage display library and identified an antibody that strongly activates cells via the CD40 receptor for potential use in HIV therapy. The anti-CD40 antibodies were converted from a single chain antibody fragment format (scFv) to an IgG format and produced in HEK293 cells, and the binding characteristics were evaluated. Next, their ability to (1) rescue a human B cell line from induced apoptosis, (2) stimulate B cell proliferation, and (3) block the CD40-CD40L interaction was determined. Finally, the most activating anti-CD40 antibody was tested for its ability to block HIV-1 infection in a monocyte-derived cell line. The different anti-CD40 antibodies, A24, B44, E30, F33, and A2-54, displayed a wide variety of binding and functional properties. In particular, B44 showed a very strong ability to activate normal human B cells and, in addition, did not block the CD40-CD40L interaction. This antibody was able to suppress HIV-1 infection in a human cell line (MonoMac 1) and may be a potential therapeutic candidate in HIV infection.