Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection
D. L. Dunn, D. C. Ewald, N. Chandan and F. B. Cerra
Previous experimental and clinical studies have demonstrated the ability of
polyclonal antibody directed against the core lipopolysaccharide
(LPS)-lipid A component of endotoxin to reduce mortality. We sought to
characterize the ability of a single murine monoclonal IgG1 antibody (8A1
MAb) to react to a variety of gram-negative microorganisms, to promote
phagocytosis, and to provide protection during experimental murine sepsis.
The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS
antigens examined by enzyme-linked immunosorbent assay. Reactivity was
highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was
promoted by this monoclonal antibody to several gram-negative bacteria,
except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced
survival during bacteremia due to either Escherichia coli 0111:B4 or
Klebsiella pneumoniae, and during endotoxemia due to all types of LPS
examined except P aeruginosa. We concluded that a single MAb with
anti-lipid A specificity was cross reactive in vitro and cross protective
in vivo. A clinical trial comparing polyclonal and monoclonal antibody in
high-risk septic patients seems warranted.
