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Immunotherapy of Gram-negative Bacterial SepsisA Single Murine Monoclonal Antibody Provides Cross-Genera Protection
David L. Dunn, MD, PhD;
David C. Ewald;
Naresh Chandan, MS;
Frank B. Cerra, MD
Arch Surg. 1986;121(1):58-62.
Abstract
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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 IgG, 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.
(Arch Surg 1986;121:58-62)
Author Affiliations
From the Department of Surgery, University of Minnesota, Minneapolis.
Footnotes
Accepted for publication Oct 1, 1985.
Read before the Fifth Annual Meeting of the Surgical Infection Society, New Orleans, April 29, 1985.
Reprint requests to Box 242 Mayo Memorial Bldg, 420 Delaware St SE, University of Minnesota, Minneapolis, MN 55455 (Dr Dunn).
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