The objective of this research program is to study and compare the biologic properties and physiologic role during gram negative bacterial sepsis of antibody preparations made using rough mutants of Escherichia coli and Salmonella minnesota as immunogens. These particular organisms express a portion of core lipopolysaccharide (LPS) extensively on their cell surface. The core portion of LPS represents a potentially available antigenic site which is shared by most, if not all, gram negative bacteria. The major thrust of this work is therefore to develop and test the protective capacity during experimental gram negative sepsis of antibody preparations which will cross react with shared antigenic structures on a wide variety of gram negative microorganisms. A two fold attack will be made on the problem: 1) polyclonal antibody preparations containing antibody of heterogeous specificity will be separated into immunoglobulin fractions and tested, and 2) monoclonal antibody preparations will be made using heterogenous antigen preparations for initial immunizations, but more purified antigen preparations for monoclonal antibody screening and selection will then be used followed by in vitro and in vivo testing. In vitro testing will consist of: 1) assessment of IgG and IgM antibody titer by an enzyme linked immunosorbent assay (ELISA), and 2) a slide phagocytosis assay to determine the opsonic character of various antibody preparations. In vivo testing will center on: 1) screening studies to define the protective capability of antibody preparations using a mouse mortality model, followed by 2) testing in a guinea pig model of gram negative bacterial sepsis during which monitoring of a variety of physiologic and immunologic parameters will take place. Mortality data and data obtained from physiologic monitoring in experimental models of gram negative bacterial sepsis will be correlated with in vitro data examining antibody titer to gram negative organisms and the ability of these antibody preparations to enhance phagocytosis of gram negative bacteria. The ability to correlate a variety of immunologic and physiology parameters with protection from the lethal affects of gram negative bacteremia should identify potential parameters which will serve to predict outcome, as well as potential antibody reagents which may prove useful in the treatment of gram negative bacterial sepsis in the clinical setting.
| Dunn, D L (1987) Antibody immunotherapy of gram-negative bacterial sepsis. Pharmacotherapy 7:S31-5 |
| Dunn, D L; Mach, P A; Dalmasso, A P et al. (1985) Metabolic effects of pretreatment with Escherichia coli J5 antiserum on guinea pig gram-negative bacterial sepsis. J Surg Res 38:298-304 |
