Generation of a protective human monoclonal for the treatment of gram-negative sepsis

Using a combination of Epstein-Barr virus transformation and cell fusion to a mouse/human heteromyeloma cell line, we have generated a human monoclonal antibody, D234, that recognizes cross-reactive determinants on the lipopoly-saccharides (LPS) of Gram-negative bacteria. Direct binding to a series of rough mutant LPSs and smooth LPSs demonstrates the broad cross-reactivity of this monoclonal. D234 inhibits Re LPS-induced chemiluminescence. In a murine model of Gram-negative sepsis, D234 given after infection significantly increases survival. This antibody may have therapeutic potential for the treatment of life-threatening Gram-negative infections in humans.