A NOVEL PEPTIDE-IGG CONJUGATE, CAP18(106-138)-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 LP S or bacterial challenge, no currently available IgG binds to LPS from all gram-negative bacteria. The ability of a peptide-IgG conjugate, C AP18(106-138)- IgG, to bind and neutralize LPS, to kill gram-negative bacteria, and to protect in a sensitized mouse model of LPS toxicity w as studied. CAP18(106-138)-IgG bound LPS from multiple gram-negative b acteria in four different binding assays. In a fluid-phase RIA, half-m aximal binding of 5 mu g/mL H-3-labeled LPS occurred at 5-10 mu g/mL C AP18(106-138)-IpG. Similar to binding with monoclonal type-specific Ig G. CAP18(106-138)-IgG neutralized LPS, as assessed by LPS-induced coag ulation of limulus amebocyte lysate and production of tumor necrosis f actor in vitro, was bactericidal for a wide range of gram-negative bac teria, and decreased LPS-induced lethality in sensitized mice. Antibac terial peptide-IgG conjugates merit further study as a novel adjunctiv e therapy for gramnegative sepsis.