SYSTEM FOR SCREENING BLOOD DONORS WITH PCR-BASED ASSAYS

DESCRIPTION: CMV is a major source of morbidity and mortality in immunocompromised individuals. This virus is responsible for a range of clinically apparent syndromes, ranging from sight-threatening retinitis in AIDS patients to life-threatening pneumonia in bone marrow and renal allograft transplant recipients. In the U.S. alone, over 4 billion dollars of health care costs are incurred as a consequence of congenital infection and disease. Our long term goal is to create a safe and efficacious live attenuated CMV vaccine that will confer protection from disease. Our approach for creating a live attenuated CMV strain is based on combining genes from two well characterized CMV strains. Genes from the Toledo strain of CMV, a virulent, wild-type virus, and Towne, an avirulent, cell culture adapted virus which causes no disease in adults, can be recombined to form effective live, attenuated virus vaccine candidates by cotransfecting overlapping cosmids into a permissive cell. By identifying genes in Toledo which contribute to its virulence and inserting these into the safe, avirulent Towne genome, a strain can be created which will confer an increased immunogenicity or replication to Towne. This new CMV will be tested to assess whether it protects recipients from CMV disease. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 69 --PROJECT NUMBER......1 R43 AI40798-01A1 INVESTIGATOR NAME/ADDRESS FY 97 LECLAIR, KENNETH P IRG/INTRAMURAL UNIT..ZRG5 PROCEPT, INC AWARD AMOUNT......... $99,638 840 MEMORIAL DRIVE CAMBRIDGE, MA 02139 PERFORMING ORGANIZATION: PROCEPT, INC. TITLE DEVELOPMENT OF LIPID VACCINES FOR TUBERCULOSIS ABSTRACT: Mycobacterium tuberculosis and other mycobacterial pathogens have reemerged as public health threats. There is an increasing incidence of drug resistant mycobacterial strains and the rate of infection of immunocompromised individuals and health care workers has escalated. Conventional TB vaccination methods have shown mixed results, leaving an urgent need for a safe and more effective vaccine. Recent research has revealed that T lymphocytes specifically recognize mycobacterial lipids presented by CD1 cell surface proteins. To develop a prophylactic or therapeutic tuberculosis vaccine, we will investigate whether M. tuberculosis mycobacterial lipids, as presented by CD1 proteins, constitute an effective vaccine in guinea pigs, the most appropriate tuberculosis small animal model. We will clone, characterize and express guinea pig CD1 genes to enable production of anti-CD1 monoclonal and polyclonal antibody reagents during Phase I. Such antibodies and cells transfected to be CD1 positive will be critical cellular and molecular tools to confirm the CD1 restricted nature and specificity of the guinea pig immune response. Phase II goals will be to identify the critical lipid component(s) of M. tuberculosis that are immunogenic in in vitro assays as well as function as effective subunit vaccines to protect guinea pigs from virulent M. tuberculosis aerosol challenge.