A receptor-mediated antigen delivery and incorporation system. Administration of alpha 2-macroglobulin-cytochrome c conjugate induced high concentrations of antibodies against cytochrome c in mice.

Specific receptors for alpha 2-macroglobulin (alpha 2M) are found on the plasma membrane of macrophages (M phi s), one of antigen presenting cells. So far, a receptor-mediated effective uptake by M phi of foreign antigens which were linked to alpha 2M has been shown to provoke a remarkable increase in the proliferation of T lymphocytes and in the production of antibodies in vitro. Such results encouraged us to develop a new type of vaccine using a receptor-mediated antigen delivery and incorporation system based on alpha 2M and its receptor interaction. In this report, we applied the system to experimental animals. Yeast cytochrome c was used as an antigen to see if the system worked in vivo as well as in vitro. Cytochrome c was conjugated to alpha 2M through the action of trypsin and intraperitoneally administered to mice. The titer induced in mice was measured by enzyme linked immunosorbent assay (ELISA). The production of antibodies against cytochrome c was significantly increased when the protein was given in conjugated forms with alpha 2M.