SCOR COMPOSITE: The major theme for this SCOR proposal is the application of new techniques in molecular biology and human monoclonal antibody production to meet the challenges of Transfusion Medicine problems of the 1990s. This program is enhanced by a multidisciplinary approach bringing together the complementary expertise of investigators from a variety of scientific biomedical disciplines and by permitting the efficient shared utilization of common Core Units. The particular problems addressed are modulation of the immune response to alloantigens and study of the pathophysiology, immunological responsiveness, transmission and prevention of several transfusion-transmitted viral diseases. In Project I, genetically engineered, soluble HLA antigens will be tested in an animal model to selectively modify recipient immune responses and prevent refractoriness to platelet transfusions. Project II will subdivide CMV seropositive donors into high vs. low risk transmission groups by polymerase chain reaction detection of viral DNA and by patterns of antibody against recombinant viral proteins; and will develop a SCID mouse system for testing anti-CMV therapeutics including human and murine monoclonal antibodies, and a modified, live CMV vaccine. Project III focuses on HIV-1 mechanisms of viral entry into susceptible cells and characterization of intracellular factors regulating viral DNA processing; and will use dendritic cell presentation of antigens to T cells to identify important HIV-1 epitopes for designing an effective AIDS vaccine. The objectives of Project IV are to define immunologically important viral epitopes of HBV, utilizing dendritic cell presentation of recombinant viral antigens to T cells in infected individuals; to test, in mice, an oral vaccine made by incorporating immunoreactive epitopes into the flagellin gene introduced into attenuated Salmonella mutant strains; and to subsequently design vaccine constructs and protocols for eventual human use. Project V will investigate the transfusion transmission and immunological responses to a new human retrovirus, 10C9; and will characterize differences between it and the closely related HTLV-I by human monoclonal antibody patterns against relevant recombinant expression libraries. Shared support for each of the investigative projects will be provided by an administrative core (A) to deal with SCOR related reports and budgetary issues; a monoclonal antibody core (B) primarily for developing and producing human monoclonal antibodies to transfusion- transmitted viruses; and a centralized cell sorter core (C) that is necessary for a wide range of immunological studies and antigen identification work in each of the five projects.
Showing the most recent 10 out of 72 publications
