A novel peptide-IgG conjugate, CAP18(106-138)-IgG, that binds and neutralizes endotoxin and kills gram-negative bacteria

J Infect Dis. 1997 Mar;175(3):621-32. doi: 10.1093/infdis/175.3.621.

Abstract

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, CAP18(106-138)-IgG, to bind and neutralize LPS, to kill gram-negative bacteria, and to protect in a sensitized mouse model of LPS toxicity was studied. CAP18(106-138)-IgG bound LPS from multiple gram-negative bacteria in four different binding assays. In a fluid-phase RIA, half-maximal binding of 5 microg/mL 3H-labeled LPS occurred at 5-10 microg/mL CAP18(106-138)-IgG, similar to binding with monoclonal type-specific IgG. CAP18(106-138)-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides*
  • Binding Sites
  • Binding, Competitive
  • Carrier Proteins / chemistry*
  • Cathelicidins
  • Cells, Cultured
  • Gram-Negative Bacteria / drug effects*
  • Immunoglobulin G / chemistry
  • Limulus Test
  • Lipopolysaccharides / chemistry*
  • Mice
  • Protein Binding
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Carrier Proteins
  • Cathelicidins
  • Immunoglobulin G
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • CAP18 lipopolysaccharide-binding protein