A Novel Peptide-IgG Conjugate, CAP18106–138-IgG, that Binds and Neutralizes Endotoxin and Kills Gram-Negative Bacteria

Although type-specific IgG directed to the O-polysaccharide antigen of bacterial lipopolysaccharide (LPS) is protective in most models of LPS or bacterial challenge, no currently available IgG binds to LPS from all gram-negative bacteria. The ability of a peptide-IgG conjugate, CAPI8106–138-IgG, to bind and neutralize LPS, to kill gram-negative bacteria, and to protect in a sensitized mouse model of LPS toxicity was studied. CAPI8106–138-IgG bound LPS from multiple gram-negative bacteria in four different binding assays. In a fluid-phase RIA, half-maximal binding of 5 µg/mL 3H-labeled LPS occurred at 5–10 µg/mL CAPI8106–138-IgG, similar to binding with monoclonal type-specific IgG. CAPI8106–138-IgG neutralized LPS, as assessed by LPS-induced coagulation of limulus amebocyte lysate and production of tumor necrosis factor in vitro, was bactericidal for a wide range of gram-negative bacteria, and decreased LPS-induced lethality in sensitized mice. Antibacterial peptide-IgG conjugates merit further study as a novel adjunctive therapy for gram-negative sepsis.