Production and Characterization of Human Monoclonal Antibodies against Gram-Negative Bacteria
In the last 20 years, Gram-negative bacteria have become the leading agents of fatal bacterial infections in hospital patients. Each year nosocomial bacteremia develops in approximately 194,000 people in the U.S.; of these about 75,000 die (Maki, 1981). This high frequency of mortality occurs despite the aggressive use of potent antibiotics. The shortcomings of antibiotic therapy may be attributed to the relative impermeability of the outer membrane of Gram-negative bacteria to the drugs and to their inability to counteract or neutralize the lethal effects of bacterial endotoxins (Ziegler et al., 1982). Chemically, the toxiphore of endotoxin is lipopolysaccharide (LPS). They have great structural diversity and are unique to Gram-negative bacteria. LPS is usually composed of three structural regions: the O-specific carbohydrate, the core, and the lipid A (Luderitz et al., 1982). The O-specific chain is typically very immunogenic and structurally heterogeneous from strain to strain. The core and lipid A portions of LPS, however, share similar structures among various strains of Gram-negative bacteria. This is particularly true in the core-lipid A junction, which almost always contains phosphate, 2-keto-3-deoxy-d-manno-octonate (KDO), and d-glucosamine (Fig. 1).
KeywordsHuman Monoclonal Antibody Human MABS Murine Antibody Gentamycin Sulfate Immune Spleen
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