Ma. Fletcher et al., A NOVEL PEPTIDE-IGG CONJUGATE, CAP18(106-138)-IGG, THAT BINDS AND NEUTRALIZES ENDOTOXIN AND KILLS GRAM-NEGATIVE BACTERIA, The Journal of infectious diseases, 175(3), 1997, pp. 621-632
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.