SBIR-STTR Award

Lipoproteins are high molecular weight, water-soluble complexes composed of lipid and one or more specific proteins. They are grouped according to their density as determined by ultracentrifugation. Plasma low-density lipoproteins (LDL) contain approximately 75 percent lipid and 25 percent protein and function as a major carrier of cholesterol. Apolipoprotein B is the structural protein moiety of LDL. An elevated level of apolipoprotein B has been reported to be a marker of coronary artery disease. In addition, reduced levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 have also been reported to be markers. HDL contains approximately 50 percent apolipoprotein with 32 percent of the lipid component being cholesterol and 65 percent of the apolipoprotein being A-1.Monoclonal antibodies with specificity for apolipoprotein B from human plasma LDL have previously been developed. Because of the role that lipoproteins play in the pathogenesis of atherosclerosis, their quantitation is important not only for metabolic studies but also for the characterization of dyslipoproteinemias. The specific aims of this project are to develop and characterize monoclonal antibodies to human apolipoprotein A-1 (Phase 1) and to use these antibodies as reference standards for the isolation or identification of apolipoprotein A-1 and as sensitive indicators of coronary artery disease (Phase II).National Heart, Lung, And Blood Institute

The major lipoprotein species of high density lipoprotein (HDL) and low density lipoprotein (LDL) are apolipoprotein A-1 and apoprotein B, respectively. Evidence suggests that there is a positive correlation between elevated plasma levels of Apo B and risk of ischemic heart disease and a negative correlation between levels of Apo A-1 (lower levels point to higher risk) with heart disease.This application is intended to develop immunoassays for use in determining plasma levels of Apo B and Apo A-1. These assays would then be used to determine a patient's risk of ischemic heart disease.The purpose of the proposed Phase II work is twofold:(1) to characterize the large panels of anti-Apo A-1 and anti-Apo B monoclonal antibodies (generated in Phase I work) with respect to all variables pertinent to immunoassay (affinity, specificity and ability to recognize 100% of Apo B or Apo A-1 in plasma)(2) to establish sensitive, specific immunoassays in the laboratory and then to adapt them into commercial kits to be sold to the clinical market.National Heart, Lung, and Blood Institute (NHLBI)