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.
Ellmark
Peter
P
Department of Immunotechnology, Lund University, Lund, Sweden. peter.ellmark@immun.lth.se
Andersson
Henrik
H
Abayneh
Sisay
S
Fenyö
Eva Maria
EM
Borrebaeck
Carl A K
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000037:antagonists & inhibitors; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D051379:Mice
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016655:HIV Core Protein p24; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D023201:CD40 Ligand